FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Parra, GI
Sosnovtsev, SV
Abente, EJ
Sandoval-Jaime, C
Bok, K
Dolan, MA
Green, KY
AF Parra, Gabriel I.
Sosnovtsev, Stanislav V.
Abente, Eugenio J.
Sandoval-Jaime, Carlos
Bok, Karin
Dolan, Michael A.
Green, Kim Y.
TI Mapping and modeling of a strain-specific epitope in the Norwalk virus
capsid inner shell
SO VIROLOGY
LA English
DT Article
DE Noroviruses; Epitope-tagging; Caliciviruses
ID BLOOD GROUP ANTIGENS; PROTEIN INTERACTIONS; HOT-SPOTS; NOROVIRUS;
VACCINE; GASTROENTERITIS; BINDING; INFECTION; ANTIBODY; SYSTEM
AB Noroviruses are diverse positive-strand RNA viruses associated with acute gastroenteritis. Cross-reactive epitopes have been mapped primarily to conserved sequences in the capsid VP1 Shell (S) domain, and strain-specific epitopes to the highly variable Protruding (P) domain. In this work, we investigated a strain-specific linear epitope defined by MAb NV10 that was raised against prototype (Genogroup 1.1) strain Norwalk virus (NV). Using peptide scanning and mutagenesis, the epitope was mapped to amino acids 21-32 (LVPEVNASDPLA) of the NV S domain, and its specificity was verified by epitope transfer and reactivity with a recombinant MAb NV10 single-chain variable fragment (scFv). Comparative structural modeling of the NV10 strain-specific and the broadly cross-reactive TV20 epitopes identified two internal non-overlapping sites in the NV shell, corresponding to variable and conserved amino acid sequences among strains, respectively. The S domain, like the P domain, contains strain-specific epitopes that contribute to the antigenic diversity among the noroviruses. Published by Elsevier Inc.
C1 [Parra, Gabriel I.; Sosnovtsev, Stanislav V.; Abente, Eugenio J.; Sandoval-Jaime, Carlos; Bok, Karin; Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Room 6318, Bethesda, MD 20892 USA.
[Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Green, KY (reprint author), NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Room 6318, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
OI Abente, Eugenio/0000-0002-3390-2786; Parra, Gabriel/0000-0002-1102-4740
FU Division of Intramural Research, NIAID, NIH, of the Department of Health
and Human Services, U.S
FX This research was funded by the Division of Intramural Research, NIAID,
NIH, of the Department of Health and Human Services, U.S.
NR 52
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PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAY
PY 2016
VL 492
BP 232
EP 241
DI 10.1016/j.virol.2016.02.019
PG 10
WC Virology
SC Virology
GA DJ4WX
UT WOS:000374209900026
PM 26971245
ER
PT J
AU Elliott, JC
Stohl, M
Wall, MM
Keyes, KM
Skodol, AE
Eaton, NR
Shmulewitz, D
Goodwin, RD
Grant, BF
Hasin, DS
AF Elliott, Jennifer C.
Stohl, Malka
Wall, Melanie M.
Keyes, Katherine M.
Skodol, Andrew E.
Eaton, Nicholas R.
Shmulewitz, Dvora
Goodwin, Renee D.
Grant, Bridget F.
Hasin, Deborah S.
TI Childhood maltreatment, personality disorders and 3-year persistence of
adult alcohol and nicotine dependence in a national sample
SO ADDICTION
LA English
DT Article
DE Alcohol; child abuse; child neglect; childhood maltreatment; chronic;
mediation; nicotine; persistence; personality disorders; substance
dependence
ID GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; SUBSTANCE USE
DISORDERS; DRUG-USE DISORDERS; IV AUDADIS-IV; UNITED-STATES;
EPIDEMIOLOGIC SURVEY; DSM-IV; INTERVENING VARIABLES; MENTAL-DISORDERS
AB Background and AimsPersistent cases of alcohol and nicotine dependence are associated with considerable morbidity and mortality, and are predicted by childhood maltreatment and personality disorders. Our aim was to test whether personality disorders (individually or conjointly) mediate the relationship between childhood maltreatment and the persistence of dependence.
DesignPersonality disorders, modeled dimensionally, were tested as mediators of the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence in participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had current alcohol and nicotine dependence in their baseline interview. Individual personality disorders were assessed in separate models. Then, those that were significant were examined jointly in multiple mediator models to determine their total and unique effects.
SettingA large, nationally representative US survey.
ParticipantsParticipants 18years who completed baseline and 3-year follow-up NESARC interviews who had baseline alcohol dependence (n=1172; 68% male) or nicotine dependence (n=4017; 52.9% male).
MeasurementsAlcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV) measures of childhood maltreatment, personality disorders and alcohol/nicotine dependence.
FindingsIndividual models indicated that many personality disorders mediated the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence (each explaining 6-46% of the total effect, Ps<0.05). In multiple mediator models, borderline and antisocial symptoms remained significant mediators, each explaining 20-37% of the total effect (Ps<0.01).
ConclusionsPersonality disorder symptoms (especially borderline and antisocial) help explain the association between childhood maltreatment and persistent alcohol and nicotine dependence.
C1 [Elliott, Jennifer C.; Keyes, Katherine M.; Goodwin, Renee D.; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Elliott, Jennifer C.; Stohl, Malka; Wall, Melanie M.; Shmulewitz, Dvora; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Elliott, Jennifer C.; Wall, Melanie M.; Skodol, Andrew E.; Shmulewitz, Dvora; Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA.
[Wall, Melanie M.] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA.
[Skodol, Andrew E.] Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA.
[Eaton, Nicholas R.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Goodwin, Renee D.] CUNY Queens Coll, Dept Psychol, Queens, NY USA.
[Goodwin, Renee D.] CUNY, Grad Ctr, Queens, NY USA.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Rockville, MD 20852 USA.
RP Hasin, DS (reprint author), Columbia Univ, New York State Psychiat Inst, 1051 Riverside Dr 123, New York, NY 10032 USA.
EM dsh2@columbia.edu
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U01AA018111,
K05AA014223, K23AA023753]; National Institute on Drug Abuse (NIDA)
[T32DA031099]; New York State Psychiatric Institute; NIAAA; NIAAA,
National Institutes of Health; NIDA
FX This study was funded by grants U01AA018111, K05AA014223, and
K23AA023753 from the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) (Drs. Hasin and Elliott); T32DA031099 from the National
Institute on Drug Abuse (NIDA) (Dr. Hasin); and the New York State
Psychiatric Institute (Drs. Hasin and Wall). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. The National
Epidemiologic Survey on Alcohol and Related Conditions was sponsored by
the NIAAA and funded in part by the Intramural Program, NIAAA, National
Institutes of Health, with additional support from NIDA. No conflict of
interest is declared.
NR 59
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U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD MAY
PY 2016
VL 111
IS 5
BP 913
EP 923
DI 10.1111/add.13292
PG 11
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DJ3HO
UT WOS:000374095600021
PM 26714255
ER
PT J
AU Shearrer, GE
O'Reilly, GA
Belcher, BR
Daniels, MJ
Goran, MI
Spruijt-Metz, D
Davis, JN
AF Shearrer, Grace E.
O'Reilly, Gillian A.
Belcher, Britini R.
Daniels, Michael J.
Goran, Michael I.
Spruijt-Metz, Donna
Davis, Jaimie N.
TI The impact of sugar sweetened beverage intake on hunger and satiety in
minority adolescents (vol 97, pg 43, 2016)
SO APPETITE
LA English
DT Correction
C1 [Shearrer, Grace E.; Davis, Jaimie N.] Univ Texas Austin, Dept Nutr, Austin, TX 78712 USA.
[O'Reilly, Gillian A.; Spruijt-Metz, Donna] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA USA.
[Belcher, Britini R.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Bethesda, MD 20892 USA.
[Daniels, Michael J.] Univ Texas Austin, Dept Stat & Computat, Austin, TX 78712 USA.
[Goran, Michael I.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Inst Prevent Res, Los Angeles, CA 90033 USA.
RP Davis, JN (reprint author), Univ Texas Austin, Dept Nutr, Austin, TX 78712 USA.
EM jaimie.davis@austin.utexas.edu
NR 1
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U1 5
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
EI 1095-8304
J9 APPETITE
JI Appetite
PD MAY 1
PY 2016
VL 100
BP 272
EP 272
DI 10.1016/j.appet.2016.02.036
PG 1
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA DJ0BK
UT WOS:000373866200032
ER
PT J
AU Bortner, CD
Scoltock, AB
Cain, DW
Cidlowski, JA
AF Bortner, C. D.
Scoltock, A. B.
Cain, D. W.
Cidlowski, J. A.
TI T-cell development of resistance to apoptosis is driven by a metabolic
shift in carbon source and altered activation of death pathways
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
ID DRUG-RESISTANCE; CANCER-CELLS; MITOCHONDRIA; MECHANISMS; RECEPTORS;
PROTEINS; PROLIFERATION; DETERMINANTS; NECROSIS; FAMILY
AB We developed a model system to investigate apoptotic resistance in T cells using osmotic stress (OS) to drive selection of death-resistant cells. Exposure of S49 (Neo) T cells to multiple rounds of OS followed by recovery of surviving cells resulted in the selection of a population of T cells (S49 (OS 4-25)) that failed to die in response to a variety of intrinsic apoptotic stimuli including acute OS, but remained sensitive to extrinsic apoptotic initiators. Genome-wide microarray analysis comparing the S49 (OS 4-25) with the parent S49 (Neo) cells revealed over 8500 differentially regulated genes, with almost 90% of those identified being repressed. Surprisingly, our data revealed that apoptotic resistance is not associated with expected changes in pro-or antiapoptotic Bcl-2 family member genes. Rather, these cells lack several characteristics associated with the initial signaling or activation of the intrinsic apoptosis pathway, including failure to increase mitochondrial-derived reactive oxygen species, failure to increase intracellular calcium, failure to deplete glutathione, failure to release cytochrome c from the mitochondria, along with a lack of induced caspase activity. The S49 (OS 4-25) cells exhibit metabolic characteristics indicative of the Warburg effect, and, despite numerous changes in mitochondria gene expression, the mitochondria have a normal metabolic capacity. Interestingly, the S49 (OS 4-25) cells have developed a complete dependence on glucose for survival, and glucose withdrawal results in cell death with many of the essential characteristics of apoptosis. Furthermore, we show that other dietary sugars such as galactose support the viability of the S49 (OS 4-25) cells in the absence of glucose; however, this carbon source sensitizes these cells to die. Our findings suggest that carbon substrate reprogramming for energy production in the S49 (OS 4-25) cells results in stimulus-specific recognition defects in the activation of intrinsic apoptotic pathways.
C1 [Bortner, C. D.; Scoltock, A. B.; Cain, D. W.; Cidlowski, J. A.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cidlowski@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX We thank Laura Wharey and Kevin Gerrish of the National Institute of
Environmental Health Sciences microarray facility for the generation and
initial analysis of the microarray data and Dr Karen Debalsi for her
helpful discussion on the Seahorse Technology. This research was
supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences.
NR 46
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U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD MAY
PY 2016
VL 23
IS 5
BP 889
EP 902
DI 10.1038/cdd.2015.156
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3SW
UT WOS:000374127500014
PM 26658018
ER
PT J
AU Macalou, S
Robey, RW
Gozzi, GJ
Shukla, S
Grosjean, I
Hegedus, T
Ambudkar, SV
Bates, SE
Di Pietro, A
AF Macalou, S.
Robey, R. W.
Gozzi, G. Jabor
Shukla, S.
Grosjean, I.
Hegedus, T.
Ambudkar, S. V.
Bates, S. E.
Di Pietro, A.
TI The linker region of breast cancer resistance protein ABCG2 is critical
for coupling of ATP-dependent drug transport
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE ABC transporter; Breast cancer resistance protein/ABCG2; ATP hydrolysis;
C motif/ABC signature; Drug efflux coupling; Specific sequence
ID CASSETTE SIGNATURE MOTIFS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN;
BINDING; GENE; INHIBITION; HYDROLYSIS; PREDICTION; MUTATIONS; POTENT
AB The ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotide-binding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an alpha-helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2-sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to mitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation. These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux.
C1 [Macalou, S.; Gozzi, G. Jabor; Di Pietro, A.] Univ Lyon 1, Equipe Labellisee Ligue 2014, BMSSI, UMR 5086 CNRS,IBCP, F-69007 Lyon, France.
[Robey, R. W.; Bates, S. E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shukla, S.; Ambudkar, S. V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Grosjean, I.] IBCP, CelluloNet Biobank BB 0033 00072, Facil SFR Biosci UMS3444 US8, F-69007 Lyon, France.
[Hegedus, T.] Semmelweis Univ, Hungarian Acad Sci, MTA SE Mol Biophys Res Grp, H-1085 Budapest, Hungary.
[Hegedus, T.] Semmelweis Univ, Dept Biophys & Radiat Biol, H-1085 Budapest, Hungary.
RP Di Pietro, A (reprint author), Univ Lyon 1, Equipe Labellisee Ligue 2014, BMSSI, UMR 5086 CNRS,IBCP, F-69007 Lyon, France.
EM a.dipietro@ibcp.fr
FU CNRS; University Lyon 1 [UMR 5086]; Ligue Nationale contre le Cancer
(Equipe Labellisee Ligue); Ligue de la Loire contre le Cancer;
Association pour la Recherche sur le Cancer; Region Rhone-Alpes
(Explora'Doc mobility program); Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research [Z01 BC010030-17];
OTKA [K 111678]; Bolyai Fellowship of the Hungarian Academy of Sciences
FX Drs. A. Ahmed-Belkacem and C. Gauthier are acknowledged for their help
in initiating the studies and performing some experiments, respectively.
This work was supported by the CNRS and University Lyon 1 (UMR 5086),
and the Ligue Nationale contre le Cancer (Equipe Labellisee Ligue 2014)
to A.D.P. S.M. was recipient of fellowships from the Ligue de la Loire
contre le Cancer, the Association pour la Recherche sur le Cancer and
the Region Rhone-Alpes (Explora'Doc mobility program with S.E.B.).
R.W.R., S.S., S.V.A. and S.E.B. were supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research (Z01 BC010030-17). The authors also thank research
funding from OTKA K 111678 and the Bolyai Fellowship of the Hungarian
Academy of Sciences to T.H.
NR 36
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U1 7
U2 16
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAY
PY 2016
VL 73
IS 9
BP 1927
EP 1937
DI 10.1007/s00018-015-2118-5
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3NH
UT WOS:000374111800012
PM 26708291
ER
PT J
AU Liu, X
Cao, YF
Ran, RX
Dong, PP
Gonzalez, FJ
XueWu
Huang, T
Chen, JX
Fu, ZW
Li, RS
Liu, YZ
Sun, HZ
Fang, ZZ
AF Liu, Xin
Cao, Yun-Feng
Ran, Rui-Xue
Dong, Pei-Pei
Gonzalez, Frank J.
XueWu
Huang, Ting
Chen, Jian-Xin
Fu, Zhi-Wei
Li, Rong-Shan
Liu, Yong-Zhe
Sun, Hong-Zhi
Fang, Zhong-Ze
TI New insights into the risk of phthalates: Inhibition of
UDP-glucuronosyltransferases (vol 144, pg 1966, 2015)
SO CHEMOSPHERE
LA English
DT Correction
C1 [Liu, Xin; Sun, Hong-Zhi] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Liaoning, Peoples R China.
[Cao, Yun-Feng; Chen, Jian-Xin] Shanghai Inst Planned Parenthood Res, Shanghai Engn & Technol Res Ctr Reprod Hlth Drug, Key Lab Contracept & Devices Res NPFPC, Shanghai, Peoples R China.
[Ran, Rui-Xue; Li, Rong-Shan] Tianjin Med Univ, Tianjin Key Lab Technol Enabling Dev Clin Therape, Sch Pharm, Tianjin, Peoples R China.
[Liu, Yong-Zhe; Fang, Zhong-Ze] Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China.
[Dong, Pei-Pei] Dalian Med Univ, Inst Integrat Med, Dalian, Peoples R China.
[XueWu; Fu, Zhi-Wei] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China.
[XueWu; Fu, Zhi-Wei] Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China.
[XueWu; Fu, Zhi-Wei] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China.
[XueWu; Fu, Zhi-Wei] Dalian Univ, Affiliated Zhongshan Hosp, Dalian 116012, Peoples R China.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Sun, HZ (reprint author), Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Liaoning, Peoples R China.; Fang, ZZ (reprint author), Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China.
EM fangzhongze@tmu.edu.cn
NR 1
TC 0
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U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0045-6535
EI 1879-1298
J9 CHEMOSPHERE
JI Chemosphere
PD MAY
PY 2016
VL 151
BP 357
EP 357
DI 10.1016/j.chemosphere.2016.03.049
PG 1
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DJ2YK
UT WOS:000374071000045
ER
PT J
AU Yang, CS
Pomerantz, H
Mannava, KA
Corwin, J
Weinstock, MA
Fleckman, P
DiGiovanna, JJ
Robinson-Bostom, L
AF Yang, Catherine S.
Pomerantz, Hyemin
Mannava, Kathleen A.
Corwin, Jessica
Weinstock, Martin A.
Fleckman, Philip
DiGiovanna, John J.
Robinson-Bostom, Leslie
TI Comparing histopathology from patients with X-linked recessive
ichthyosis and autosomal recessive congenital ichthyosis with
transglutaminase 1 mutation: A report from the National Registry for
Ichthyosis and Related Skin Disorders
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
ID HISTOLOGY; VULGARIS
C1 [Yang, Catherine S.; Weinstock, Martin A.; Robinson-Bostom, Leslie] Brown Univ, Alpert Med Sch, Dept Dermatol, 593 Eddy St APC 1018, Providence, RI 02903 USA.
[Pomerantz, Hyemin; Weinstock, Martin A.] VA Med Ctr, Dermatoepidemiol Unit, Providence, RI USA.
[Mannava, Kathleen A.] Wake Forest Sch Med, Dept Pathol, Winston Salem, NC USA.
[Corwin, Jessica] Vacaville Med Ctr, Dept Dermatol, Vacaville, CA USA.
[Fleckman, Philip] Univ Washington, Div Dermatol, Seattle, WA 98195 USA.
[DiGiovanna, John J.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Yang, CS (reprint author), Brown Univ, Alpert Med Sch, Dept Dermatol, 593 Eddy St APC 1018, Providence, RI 02903 USA.
EM catherine_yang@brown.edu
FU Intramural NIH HHS [Z99 CA999999]; NCATS NIH HHS [UL1TR000423, UL1
TR000423]; NCRR NIH HHS [M01 RR000037]; NIAMS NIH HHS [N01-AR-1-2252,
N01 AR042216]
NR 5
TC 0
Z9 0
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD MAY
PY 2016
VL 74
IS 5
BP 1008
EP 1010
DI 10.1016/j.jaad.2015.12.027
PG 4
WC Dermatology
SC Dermatology
GA DJ3PF
UT WOS:000374117100033
PM 27085231
ER
PT J
AU Miller, JG
Li, M
Mazilu, D
Hunt, T
Horvath, KA
AF Miller, Justin G.
Li, Ming
Mazilu, Dumitru
Hunt, Tim
Horvath, Keith A.
TI Real-time magnetic resonance imaging-guided transcatheter aortic valve
replacement
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
DE transcatheter aortic valve replacement; real-time magnetic resonance
image; swine animal model; Medtronic CoreValve
ID 3-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY;
INTERACTIVE MRI; IN-VITRO; IMPLANTATION; DISEASE; STENOSIS; SURGERY;
BIOPROSTHESIS; PROSTHESIS
AB Objectives: To demonstrate the feasibility of Real-time magnetic resonance imaging (rtMRI) guided transcatheter aortic valve replacement (TAVR) with an active guidewire and anMRI compatible valve delivery catheter system in a swine model.
Methods: The CoreValve system was minimally modified to be MRI-compatible by replacing the stainless steel components with fluoroplastic resin and high-density polyethylene components. Eight swine weighing 60-90 kg underwent rtMRI-guided TAVR with an active guidewire through a left subclavian approach.
Results: Two imaging planes (long-axis view and short-axis view) were used simultaneously for real-time imaging during implantation. Successful deployment was performed without rapid ventricular pacing or cardiopulmonary bypass. Postdeployment images were acquired to evaluate the final valve position in addition to valvular and cardiac function.
Conclusions: Our results show that the CoreValve can be easily and effectively deployed through a left subclavian approach using rtMRI guidance, a minimally modified valve delivery catheter system, and an active guidewire. This method allows superior visualization before deployment, thereby allowing placement of the valve with pinpoint accuracy. rtMRI has the added benefit of the ability to perform immediate postprocedural functional assessment, while eliminating the morbidity associated with radiation exposure, rapid ventricular pacing, contrast media renal toxicity, and a more invasive procedure. Use of a commercially available device brings this rtMRI-guided approach closer to clinical reality.
C1 [Miller, Justin G.; Li, Ming; Mazilu, Dumitru; Hunt, Tim; Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Horvath, KA (reprint author), 10 Ctr Dr,Bldg 10,Rm B1D47, Bethesda, MD 20892 USA.
EM horvathka@mail.nih.gov
FU National Heart, Lung and Blood Institute, Division of Intramural
Research
FX This research was funded by the National Heart, Lung and Blood
Institute, Division of Intramural Research.
NR 51
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U1 2
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD MAY
PY 2016
VL 151
IS 5
BP 1269
EP 1277
DI 10.1016/j.jtcvs.2015.11.024
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DJ3PO
UT WOS:000374118100013
PM 26725711
ER
PT J
AU Miller, JG
Li, M
Mazilu, D
Hunt, T
Horvath, KA
AF Miller, Justin G.
Li, Ming
Mazilu, Dumitru
Hunt, Tim
Horvath, Keith A.
TI Robot-assisted real-time magnetic resonance image-guided transcatheter
aortic valve replacement
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
DE robot-assisted transcatheter aortic valve replacement; real-time
magnetic resonance image; swine animal model
ID 3-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY;
INTERACTIVE MRI; IMPLANTATION; BIOPROSTHESIS; STENOSIS; GUIDANCE;
DISEASE; DEVICES; SURGERY
AB Background: Real-time magnetic resonance imaging (rtMRI)-guided transcatheter aortic valve replacement (TAVR) offers improved visualization, real-time imaging, and pinpoint accuracy with device delivery. Unfortunately, performing a TAVR in a MRI scanner can be a difficult task owing to limited space and an awkward working environment. Our solution was to design a MRI-compatible robot-assisted device to insert and deploy a self-expanding valve from a remote computer console. We present our preliminary results in a swine model.
Methods: We used an MRI-compatible robotic arm and developed a valve delivery module. A 12-mm trocar was inserted in the apex of the heart via a subxiphoid incision. The delivery device and nitinol stented prosthesis were mounted on the robot. Two continuous real-time imaging planes provided a virtual real-time 3-dimensional reconstruction. The valve was deployed remotely by the surgeon via a graphic user interface.
Results: In this acute nonsurvival study, 8 swine underwent robot-assisted rtMRI TAVR for evaluation of feasibility. Device deployment took a mean of 61 +/- 5 seconds. Postdeployment necropsy was performed to confirm correlations between imaging and actual valve positions.
Conclusions: These results demonstrate the feasibility of robotic-assisted TAVR using rtMRI guidance. This approach may eliminate some of the challenges of performing a procedure while working inside of an MRI scanner, and may improve the success of TAVR. It provides superior visualization during the insertion process, pinpoint accuracy of deployment, and, potentially, communication between the imaging device and the robotic module to prevent incorrect or misaligned deployment.
C1 [Miller, Justin G.; Li, Ming; Mazilu, Dumitru; Hunt, Tim; Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Horvath, KA (reprint author), 10 Ctr Dr,Bldg 10,Rm B1D47, Bethesda, MD 20892 USA.
EM horvathka@mail.nih.gov
FU National Heart, Lung and Blood Institute
FX This research received intramural funding from the National Heart, Lung
and Blood Institute.
NR 40
TC 1
Z9 1
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD MAY
PY 2016
VL 151
IS 5
BP 1407
EP 1412
DI 10.1016/j.jtcvs.2015.11.047
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DJ3PO
UT WOS:000374118100041
PM 26778373
ER
PT J
AU Mok, KY
Sheerin, U
Simon-Sanchez, J
Salaka, A
Chester, L
Escott-Price, V
Mantripragada, K
Doherty, KM
Noyce, AJ
Mencacci, NE
Lubbe, SJ
Williams-Gray, CH
Barker, RA
Van Dijk, KD
Berendse, HW
Heutink, P
Corvol, JC
Cormier, F
Lesage, S
Brice, A
Brockmann, K
Schulte, C
Gasser, T
Foltynie, T
Limousin, P
Morrison, KE
Clarke, CE
Sawcer, S
Warner, TT
Lees, AJ
Morris, HR
Nalls, MA
Singleton, AB
Hardy, J
Abramov, AY
Plagnol, V
Williams, NM
Wood, NW
AF Mok, Kin Y.
Sheerin, Una
Simon-Sanchez, Javier
Salaka, Afnan
Chester, Lucy
Escott-Price, Valentina
Mantripragada, Kiran
Doherty, Karen M.
Noyce, Alastair J.
Mencacci, Niccolo E.
Lubbe, Steven J.
Williams-Gray, Caroline H.
Barker, Roger A.
Van Dijk, Karin D.
Berendse, Henk W.
Heutink, Peter
Corvol, Jean-Christophe
Cormier, Florence
Lesage, Suzanne
Brice, Alexis
Brockmann, Kathrin
Schulte, Claudia
Gasser, Thomas
Foltynie, Thomas
Limousin, Patricia
Morrison, Karen E.
Clarke, Carl E.
Sawcer, Stephen
Warner, Tom T.
Lees, Andrew J.
Morris, Huw R.
Nalls, Mike A.
Singleton, Andrew B.
Hardy, John
Abramov, Andrey Y.
Plagnol, Vincent
Williams, Nigel M.
Wood, Nicholas W.
CA Int Parkinson's Dis Genomics
TI Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined
analysis of genome-wide association data
SO LANCET NEUROLOGY
LA English
DT Article
ID CLINICAL-FEATURES; SCHIZOPHRENIA; METAANALYSIS; DIAGNOSIS;
IDENTIFICATION; COOCCURRENCE; GENETICS; RISK; LOCI
AB Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2.
Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients.
Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0.00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0.001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32.0-55.5; mean 42.1 years [SD 11.9]) than in those who did not carry a deletion (median 61 years, 95% CI 60.5-61.0; mean 60.3 years [SD 12.8]). A 22q11.2 deletion was present in more patients with early-onset (p<0.0001) and late-onset Parkinson's disease (p=0.016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0.005).
Interpretation Clinicians should be alert to the possibility of 22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both. Copyright (C) Mok et al. Open Access article distributed under the terms of CC BY.
C1 [Mok, Kin Y.; Sheerin, Una; Noyce, Alastair J.; Mencacci, Niccolo E.; Hardy, John; Abramov, Andrey Y.; Wood, Nicholas W.] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Doherty, Karen M.; Noyce, Alastair J.; Warner, Tom T.; Lees, Andrew J.; Hardy, John] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England.
[Foltynie, Thomas; Limousin, Patricia] UCL Inst Neurol, Sobell Dept Motor Neurosci, London WC1N 3BG, England.
[Lubbe, Steven J.; Morris, Huw R.] UCL Inst Neurol, Dept Clin Neurosci, London WC1N 3BG, England.
[Mok, Kin Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China.
[Simon-Sanchez, Javier] Hertie Inst Clin Brain Res HIH, Genet & Epigenet Neurodegenerat, Tubingen, Germany.
[Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas] Hertie Inst Clin Brain Res HIH, Dept Neurodegenerat Dis, Tubingen, Germany.
[Simon-Sanchez, Javier] German Ctr Neurodegenerat Dis DZNE, Genet & Epigenet Neurodegenerat, Tubingen, Germany.
[Heutink, Peter] German Ctr Neurodegenerat Dis DZNE, Genome Biol Neurodegenerat Dis, Tubingen, Germany.
[Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany.
[Salaka, Afnan; Chester, Lucy; Escott-Price, Valentina; Mantripragada, Kiran; Williams, Nigel M.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales.
[Salaka, Afnan] Umm Al Qura Univ, Fac Appl Med Sci, Med Genet & Lab Med Dept, Mecca, Saudi Arabia.
[Doherty, Karen M.] Royal Victoria Hosp, Dept Reg Neurosci, Belfast BT12 6BA, Antrim, North Ireland.
[Williams-Gray, Caroline H.; Barker, Roger A.] Univ Cambridge, Dept Clin Neurosci, John van Geest Ctr Brain Repair, Forvie Site, Cambridge, England.
[Sawcer, Stephen] Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge, England.
[Van Dijk, Karin D.; Berendse, Henk W.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis] Univ Paris 06, Sorbonne Univ, French Natl Ctr Sci Res CNRS,Inst Cerveau, Res Unit U1127,INSERM,Res Unit UMR 7225, Paris, France.
[Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis] Univ Paris 06, Sorbonne Univ, Inst Cerveau, Res Unit UMR S 1127, Paris, France.
[Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis] Moelle Epiniere Brain & Spine Inst ICM, Paris, France.
[Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis] INSERM, Clin Invest Ctr, U1422, Paris, France.
[Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Ctr Invest Clin Pitie Neurosci, Paris, France.
[Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas] Univ Tubingen, Dept Neurodegenerat Dis, Tubingen, Germany.
[Morrison, Karen E.] Univ Birmingham, Coll Med & Dent Sci, Inst Clin Sci, Birmingham, W Midlands, England.
[Clarke, Carl E.] Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Nalls, Mike A.; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Plagnol, Vincent] UCL Genet Inst, London, England.
RP Wood, NW (reprint author), UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.; Williams, NM (reprint author), Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales.
EM williamsnm@cf.ac.uk; n.wood@ucl.ac.uk
RI Hardy, John/C-2451-2009; Mok, Kin/F-5860-2012; Lubbe,
Steven/L-8261-2013; Singleton, Andrew/C-3010-2009; Morris,
Huw/B-8527-2008; Abramov, Andrey/H-9053-2012; Warner,
Thomas/A-1454-2013; Wood, Nicholas/C-2505-2009; corvol,
jean-christophe/I-6387-2012;
OI Morris, Huw/0000-0002-5473-3774; Abramov, Andrey/0000-0002-7646-7235;
Warner, Thomas/0000-0001-6195-6995; Wood, Nicholas/0000-0002-9500-3348;
corvol, jean-christophe/0000-0001-7325-0199; Escott-Price,
Valentina/0000-0003-1784-5483
FU UK Medical Research Council; UK Wellcome Trust; Parkinson's UK; Patrick
Berthoud Trust; National Institutes of Health; Investissements d'Avenir
[ANR-10-IAIHU-06]; Dutch Parkinson Foundation (Parkinson Vereniging);
Neuroscience Campus Amsterdam; National Institute for Health Research,
National Institute on Aging, National Institutes of Health
FX UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick
Berthoud Trust, National Institutes of Health, "Investissements
d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson
Vereniging), Neuroscience Campus Amsterdam, National Institute for
Health Research, National Institute on Aging, National Institutes of
Health.
NR 47
TC 5
Z9 5
U1 9
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAY
PY 2016
VL 15
IS 6
BP 585
EP 596
DI 10.1016/S1474-4422(16)00071-5
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA DI9PW
UT WOS:000373835900017
PM 27017469
ER
PT J
AU Zou, T
Jaladanki, SK
Liu, L
Xiao, L
Chung, HK
Wang, JY
Xu, Y
Gorospe, M
Wang, JY
AF Zou, Tongtong
Jaladanki, Suraj K.
Liu, Lan
Xiao, Lan
Chung, Hee Kyoung
Wang, Jun-Yao
Xu, Yan
Gorospe, Myriam
Wang, Jian-Ying
TI y H19 Long Noncoding RNA Regulates Intestinal Epithelial Barrier
Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID IMPRINTED GENE NETWORK; MESSENGER-RNA; TIGHT JUNCTION; E-CADHERIN;
CANCER METASTASIS; PROCESSING BODIES; TUMOR-SUPPRESSOR; CELL-MIGRATION;
TRANSLATION; GROWTH
AB The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. The H19 long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report that H19 plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675). H19 overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressing H19 prevented the stimulation of miR-675 processing from H19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate that H19 interacts with HuR and regulates the intestinal epithelial barrier function via the H19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally.
C1 [Zou, Tongtong; Jaladanki, Suraj K.; Liu, Lan; Xiao, Lan; Chung, Hee Kyoung; Wang, Jun-Yao; Xu, Yan; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Zou, Tongtong; Jaladanki, Suraj K.; Liu, Lan; Xiao, Lan; Chung, Hee Kyoung; Wang, Jun-Yao; Xu, Yan; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Gorospe, Myriam] NIA, Genet Lab, IRP, NIH, Baltimore, MD 21224 USA.
RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.; Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.; Wang, JY (reprint author), Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
EM jwang@smail.umaryland.edu
FU VA Merit Review Award; HHS \ National Institutes of Health (NIH)
[DK57819, DK61972, DK68491]
FX This work, including the efforts of Jian-Ying Wang, was funded by VA
Merit Review Award. This work, including the efforts of Jian-Ying Wang,
was funded by HHS vertical bar National Institutes of Health (NIH)
(DK57819, DK61972, and DK68491).
NR 64
TC 4
Z9 4
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2016
VL 36
IS 9
BP 1332
EP 1341
DI 10.1128/MCB.01030-15
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3MZ
UT WOS:000374110900002
PM 26884465
ER
PT J
AU Patial, S
Stumpo, DJ
Young, WS
Ward, JM
Flake, GP
Blackshear, PJ
AF Patial, Sonika
Stumpo, Deborah J.
Young, W. Scott, III
Ward, James M.
Flake, Gordon P.
Blackshear, Perry J.
TI Effects of Combined Tristetraprolin/Tumor Necrosis Factor Receptor
Deficiency on the Splenic Transcriptome
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-BINDING PROTEINS; ZINC-FINGER DOMAIN; MESSENGER-RNA;
IRON-DEFICIENCY; GENE-EXPRESSION; CHRONIC DISEASE; TNF-ALPHA;
DEADENYLATION; DEGRADATION; HOMEOSTASIS
AB Tristetraprolin (TTP) acts by binding to AU-rich elements in certain mRNAs, such as tumor necrosis factor (TNF) mRNA, and increasing their decay rates. TTP knockout mice exhibit a profound inflammatory syndrome that is largely due to increased TNF levels. Although TTP's effects on gene expression have been well studied in cultured cells, little is known about its functions in intact tissues. We performed deep RNA sequencing on spleens from TTP knockout mice that were also deficient in both TNF receptors ("triple knockout" mice) to remove the secondary effects of excess TNF activity. To help identify posttranscriptionally regulated transcripts, we also compared changes in mature mRNA levels to levels of transiently expressed pre-mRNA. In the triple knockout spleens, levels of 3,014 transcripts were significantly affected by 1.5-fold or more, but only a small fraction exhibited differential mRNA/pre-mRNA changes suggestive of increased mRNA stability. Transferrin receptor mRNA, which contains two highly conserved potential TTP binding sites, was significantly upregulated relative to its pre-mRNA. This was reflected in increased transferrin receptor expression and increased splenic iron/hemosiderin deposition. Our results suggest that TTP deficiency has profound effects on the splenic transcriptome, even in the absence of secondary increases in TNF activity.
C1 [Patial, Sonika; Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
[Ward, James M.] NIEHS, Integrat Bioinformat, POB 12233, Res Triangle Pk, NC 27709 USA.
[Flake, Gordon P.] NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA.
[Young, W. Scott, III] NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
EM black009@niehs.nih.gov
RI Young, W Scott/A-9333-2009
OI Young, W Scott/0000-0001-6614-5112
FU NIH, National Institute of Environmental Health Sciences; National
Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences and National
Institute of Mental Health.
NR 47
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2016
VL 36
IS 9
BP 1395
EP 1411
DI 10.1128/MCB.01068-15
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3MZ
UT WOS:000374110900007
PM 26976640
ER
PT J
AU Kiss, A
Koppel, AC
Anders, J
Cataisson, C
Yuspa, SH
Blumenberg, M
Efimova, T
AF Kiss, Alexi
Koppel, Aaron C.
Anders, Joanna
Cataisson, Christophe
Yuspa, Stuart H.
Blumenberg, Miroslav
Efimova, Tatiana
TI Keratinocyte p38 loss inhibits Ras-induced tumor formation, while
systemic p38 loss enhances skin inflammation in the early phase of
chemical carcinogenesis in mouse skin
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE p38; knockout mice; orthotopic skin grafts; skin inflammation; p38
ID ACTIVATED PROTEIN-KINASE; GENE-EXPRESSION; CELL-TRANSFORMATION; CANCER
DEVELOPMENT; P38-DELTA; DIFFERENTIATION; MICE; P38-GAMMA; MORPHOGENESIS;
TUMORIGENESIS
AB p38 expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38 in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38 exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38 gene ablation inhibited the growth of tumors generated from v-ras(Ha)-transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38 is required for Ras-induced tumorigenesis. Gene expression profiling of v-ras(Ha)-transformed p38-null keratinocytes revealed transcriptional changes associated with cellular responses linked to tumor suppression, such as reduced proliferation and increased differentiation, cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge, modeling the initial stages of chemical skin carcinogenesis treatment, elicited an enhanced inflammation in p38-null skin compared with skin of wild-type mice, as assessed by measuring the expression of pro-inflammatory cytokines, including IL-1, IL-6, IL-17, and TNF. Additionally, p38-null skin and p38-null keratinocytes exhibited increased p38 activation and signaling in response to acute inflammatory challenges, suggesting a role for p38 in stimulating the elevated inflammatory response in p38-null skin during the initial phases of the DMBA/TPA treatment compared with similarly treated p38(+/+) skin. Altogether, our results indicate that p38 signaling regulates skin carcinogenesis not only by keratinocyte cell-autonomous mechanisms, but also by influencing the interaction between between the epithelial compartment of the developing skin tumor and its stromal microenvironment. (c) 2015 Wiley Periodicals, Inc.
C1 [Kiss, Alexi; Koppel, Aaron C.; Efimova, Tatiana] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA.
[Anders, Joanna; Cataisson, Christophe; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Blumenberg, Miroslav] NYU, Sch Med, RO Perelman Dept Dermatol, New York, NY USA.
RP Efimova, T (reprint author), Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA.; Efimova, T (reprint author), Washington Univ, Sch Med, Div Dermatol, Dept Internal Med, Campus Box 8123,660 S Euclid Ave, St Louis, MO 63110 USA.
FU National Institutes of Health [R01 CA133038]; Center for Cancer Research
of the National Cancer Institute
FX Grant sponsor: National Institutes of Health; Grant number: R01
CA133038; Grant sponsor: Center for Cancer Research of the National
Cancer Institute
NR 51
TC 0
Z9 0
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
EI 1098-2744
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD MAY
PY 2016
VL 55
IS 5
BP 563
EP 574
DI 10.1002/mc.22303
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA DJ3IA
UT WOS:000374096800013
PM 25753147
ER
PT J
AU Poletto, M
Malfatti, MC
Dorjsuren, D
Scognamiglio, PL
Marasco, D
Vascotto, C
Jadhav, A
Maloney, DJ
Wilson, DM
Simeonov, A
Tell, G
AF Poletto, Mattia
Malfatti, Matilde C.
Dorjsuren, Dorjbal
Scognamiglio, Pasqualina L.
Marasco, Daniela
Vascotto, Carlo
Jadhav, Ajit
Maloney, David J.
Wilson, David M., III
Simeonov, Anton
Tell, Gianluca
TI Inhibitors of the apurinic/apyrimidinic endonuclease 1
(APE1)/nucleophosmin (NPM1) interaction that display anti-tumor
properties
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE APE1; NPM1; protein; protein interaction; small molecule; combination
therapy
ID BASE EXCISION-REPAIR; CRITICAL LYSINE RESIDUES; N-TERMINAL DOMAIN;
HEPATOCELLULAR-CARCINOMA; DNA-REPAIR; PROGNOSTIC-SIGNIFICANCE; PROTEIN
INTERACTIONS; PROXIMITY LIGATION; CELLS; APE1
AB The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas. (c) 2015 Wiley Periodicals, Inc.
C1 [Poletto, Mattia; Malfatti, Matilde C.; Vascotto, Carlo; Tell, Gianluca] Univ Udine, Dept Med & Biol Sci, Ple Kolbe 4, I-33100 Udine, Italy.
[Dorjsuren, Dorjbal; Jadhav, Ajit; Maloney, David J.; Simeonov, Anton] Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, NIH, Bethesda, MD USA.
[Scognamiglio, Pasqualina L.; Marasco, Daniela] Univ Naples Federico II, CIRPEB, Dept Pharm, Naples, Italy.
[Scognamiglio, Pasqualina L.] IIT, Ctr Adv Biomat Healthcare CRIB, Naples, Italy.
[Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Tell, G (reprint author), Univ Udine, Dept Med & Biol Sci, Ple Kolbe 4, I-33100 Udine, Italy.; Simeonov, A (reprint author), Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, NIH, Bethesda, MD USA.
OI vascotto, carlo/0000-0003-4431-029X; Tell, Gianluca/0000-0001-8845-6448
FU Associazione Italiana per la Ricerca sul Cancro [IG10269, IG14038];
European Regional development Fund (ERDF); National Funds by the
Autonomous Region Friuli Venezia Giulia, in quality of Managing
Authority; Crossborder cooperation program Italy-Slovenia; Intramural
Research Program at the NIH, National Institute on Aging; Intramural
Research Program of the National Center for Advancing Translational
Sciences; Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research [U54MH08468]
FX Grant sponsor: The Associazione Italiana per la Ricerca sul Cancro;
Grant number: IG10269 and IG14038; Grant sponsor: The European Regional
development Fund (ERDF) and the National Funds, implemented by the
Autonomous Region Friuli Venezia Giulia, in quality of Managing
Authority, Grant name: The Crossborder cooperation program
Italy-Slovenia 2007-2013; Grant sponsor: The Intramural Research Program
at the NIH, National Institute on Aging; Grant sponsor: The Intramural
Research Program of the National Center for Advancing Translational
Sciences and the Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research; Grant number:
U54MH08468
NR 52
TC 9
Z9 9
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
EI 1098-2744
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD MAY
PY 2016
VL 55
IS 5
BP 688
EP 704
DI 10.1002/mc.22313
PG 17
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA DJ3IA
UT WOS:000374096800023
PM 25865359
ER
PT J
AU Gunduz-Cinar, O
Flynn, S
Brockway, E
Kaugars, K
Baldi, R
Ramikie, TS
Cinar, R
Kunos, G
Patel, S
Holmes, A
AF Gunduz-Cinar, Ozge
Flynn, Shaun
Brockway, Emma
Kaugars, Katherine
Baldi, Rita
Ramikie, Teniel S.
Cinar, Resat
Kunos, George
Patel, Sachin
Holmes, Andrew
TI Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID ACID AMIDE HYDROLASE; POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE
INHIBITORS; ANTIDEPRESSANT-LIKE ACTIVITY; CB1 CANNABINOID RECEPTORS;
ELEVATED PLUS-MAZE; BASOLATERAL AMYGDALA; TRANSLATIONAL EVIDENCE;
PREFRONTAL CORTEX; NEURONAL CIRCUITS
AB Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitator), effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired I 29S1/Sv I mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB I receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.
C1 [Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
[Baldi, Rita; Ramikie, Teniel S.; Patel, Sachin] Vanderbilt Univ, Med Ctr, Dept Psychiat & Mol Physiol & Biophys, Nashville, TN USA.
[Cinar, Resat; Kunos, George] NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
RP Gunduz-Cinar, O; Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM ozge.gunduzcinar@nih.gov; holmesan@mail.nih.gov
OI CINAR, RESAT/0000-0002-8597-7253
FU NIAAA Intramural Research Program; NIH [MH100096, MH09012]; Vanderbilt
University
FX This research was supported by the NIAAA Intramural Research Program and
NIH Grants MH100096 and MH09012 (to SP). SP receives research contract
support from Lundbeck Pharmaceuticals; however, the current work was
supported entirely by the NIH and Vanderbilt University. The authors
declare no conflict of interest.
NR 80
TC 4
Z9 4
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2016
VL 41
IS 6
BP 1598
EP 1609
DI 10.1038/npp.2015.318
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DJ1MD
UT WOS:000373966000018
PM 26514583
ER
PT J
AU Mezey, E
AF Mezey, Eva
TI On the origin of blood cells - hematopoiesis revisited
SO ORAL DISEASES
LA English
DT Editorial Material
ID STEM-CELLS; PROGENITORS; IDENTIFICATION; PROLIFERATION
C1 [Mezey, Eva] NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA.
RP Mezey, E (reprint author), NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA.
FU Intramural NIH HHS [, Z01 DE000714-04]
NR 16
TC 0
Z9 0
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD MAY
PY 2016
VL 22
IS 4
BP 247
EP 248
DI 10.1111/odi.12445
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DJ2PH
UT WOS:000374046600001
PM 26802784
ER
PT J
AU Gupta, R
Dhyani, M
Kendzerska, T
Pandi-Perumal, SR
BaHammam, AS
Srivanitchapoom, P
Pandey, S
Hallett, M
AF Gupta, R.
Dhyani, M.
Kendzerska, T.
Pandi-Perumal, S. R.
BaHammam, A. S.
Srivanitchapoom, P.
Pandey, S.
Hallett, M.
TI Restless legs syndrome and pregnancy: prevalence, possible
pathophysiological mechanisms and treatment
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Review
DE pregnancy; prevalence; restless legs syndrome; treatment
ID WILLIS-EKBOM DISEASE; LIMB MOVEMENT-DISORDER; INTRAVENOUS IRON SUCROSE;
OBSTRUCTIVE SLEEP-APNEA; VITAMIN-D DEFICIENCY; LOW SERUM FERRITIN;
PARKINSONS-DISEASE; PRIMARY HYPERPARATHYROIDISM; DIAGNOSTIC-CRITERIA;
CONTROLLED TRIAL
AB Restless legs syndrome (RLS) is a common sleep disorder that may be associated with pregnancy. Studies have found that the prevalence of RLS among pregnant women ranged from 10 to 34%. Typically, there is complete remission of symptoms soon after parturition; however, in some patients, they may continue postpartum. RLS has been shown to be associated with a number of complications in pregnancy including preeclampsia and increased incidence of Cesarean sections. Although multiple hypotheses have been proposed to explain this association, each individual hypothesis cannot completely explain the whole pathogenesis. Present understanding suggests that a strong family history, low serum iron and ferritin level, and high estrogen level during pregnancy might play important roles. Vitamin D deficiency and calcium metabolism may also play a role. Medical treatment of RLS during pregnancy is difficult and challenging considering the risks to mother and fetus. However, in some cases, the disease may be severe enough to require treatment.
C1 [Gupta, R.; Dhyani, M.] Himalayan Inst Med Sci, Dept Psychiat, Dehra Dun 248016, Uttar Pradesh, India.
[Gupta, R.; Dhyani, M.] Himalayan Inst Med Sci, Sleep Clin, Dehra Dun 248016, Uttar Pradesh, India.
[Kendzerska, T.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada.
[Pandi-Perumal, S. R.] Somnogen Canada Inc, Toronto, ON, Canada.
[BaHammam, A. S.] King Saud Univ, Univ Sleep Disorders Ctr, Coll Med, Dept Med, Riyadh, Saudi Arabia.
[BaHammam, A. S.] Natl Plan Sci Technol & Innovat Riyadh, Strateg Technol Program, Riyadh, Saudi Arabia.
[Srivanitchapoom, P.; Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Srivanitchapoom, P.] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Med, Bangkok 10700, Thailand.
[Pandey, S.] Govind Ballabh Pant Inst Postgrad Med Educ & Res, New Delhi, India.
RP Gupta, R (reprint author), Himalayan Inst Med Sci, Dept Psychiat, Dehra Dun 248016, Uttar Pradesh, India.; Gupta, R (reprint author), Himalayan Inst Med Sci, Sleep Clin, Dehra Dun 248016, Uttar Pradesh, India.
EM sleepdoc.ravi@gmail.com
RI BaHammam, Ahmed/B-9037-2008; Seithikurippu R, Pandi-Perumal/Q-8281-2016;
OI BaHammam, Ahmed/0000-0002-1706-6167; Seithikurippu R,
Pandi-Perumal/0000-0002-8686-7259; Gupta, Ravi/0000-0003-2583-563X;
Kendzerska, Tetyana/0000-0002-5301-1796
NR 98
TC 2
Z9 2
U1 6
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0001-6314
EI 1600-0404
J9 ACTA NEUROL SCAND
JI Acta Neurol. Scand.
PD MAY
PY 2016
VL 133
IS 5
BP 320
EP 329
DI 10.1111/ane.12520
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA DI8TH
UT WOS:000373774300001
PM 26482928
ER
PT J
AU McPherron, AC
AF McPherron, A. C.
TI The ups and downs of exercise and insulin sensitivity: a role for the
myokine myostatin in glucose metabolism?
SO ACTA PHYSIOLOGICA
LA English
DT Editorial Material
ID EXPRESSION
C1 [McPherron, A. C.] NIDDK, Bethesda, MD 20892 USA.
[McPherron, A. C.] MyoTherapeutics, Silver Spring, MD USA.
RP McPherron, AC (reprint author), NIDDK, Bethesda, MD 20892 USA.; McPherron, AC (reprint author), MyoTherapeutics, Silver Spring, MD USA.
EM mcpherrona@niddk.nih.gov
NR 11
TC 0
Z9 0
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1748-1708
EI 1748-1716
J9 ACTA PHYSIOL
JI Acta Physiol.
PD MAY
PY 2016
VL 217
IS 1
BP 6
EP 10
DI 10.1111/apha.12650
PG 5
WC Physiology
SC Physiology
GA DI4UM
UT WOS:000373494900002
PM 26751052
ER
PT J
AU Schwartz, LP
Silberberg, A
Casey, AH
Paukner, A
Suomi, SJ
AF Schwartz, Lindsay P.
Silberberg, Alan
Casey, Anna H.
Paukner, Annika
Suomi, Stephen J.
TI Scaling reward value with demand curves versus preference tests
SO ANIMAL COGNITION
LA English
DT Article
DE Behavioral economics; Exponential model of demand; Choice; Monkeys
ID MONKEYS CEBUS-APELLA; CAPUCHIN MONKEYS; INEQUITY AVERSION; REFLEX
STRENGTH; FOOD; GRATIFICATION; ECONOMICS; CHOICE; DRIVE; DELAY
AB In Experiment 1, six capuchins lifted a weight during a 10-min session to receive a food piece. Across conditions, the weight was increased across six different amounts for three different food types. The number of food pieces obtained as a function of the weight lifted was fitted by a demand equation that is hypothesized to quantify food value. For most subjects, this analysis showed that the three food types differed little in value. In Experiment 2, these monkeys were given pairwise choices among these food types. In 13 of 18 comparisons, preferences at least equaled a 3-to-1 ratio; in seven comparisons, preference was absolute. There was no relation between values based on degree of preference versus values based on the demand equation. When choices in the present report were compared to similar data with these subjects from another study, between-study lability in preference emerged. This outcome contrasts with the finding in demand analysis that test-retest reliability is high. We attribute the unreliability and extreme assignment of value based on preference tests to high substitutability between foods. We suggest use of demand analysis instead of preference tests for studies that compare the values of different foods. A better strategy might be to avoid manipulating value by using different foods. Where possible, value should be manipulated by varying amounts of a single food type because, over an appropriate range, more food is consistently more valuable than less. Such an approach would be immune to problems in between-food substitutability.
C1 [Schwartz, Lindsay P.; Silberberg, Alan; Casey, Anna H.] Amer Univ, Dept Psychol, Washington, DC 20016 USA.
[Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Poolesville, MD USA.
RP Schwartz, LP (reprint author), Amer Univ, Dept Psychol, Washington, DC 20016 USA.
EM lindsaypschwartz@gmail.com
FU Intramural NIH HHS [Z99 HD999999]
NR 25
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1435-9448
EI 1435-9456
J9 ANIM COGN
JI Anim. Cogn.
PD MAY
PY 2016
VL 19
IS 3
BP 631
EP 641
DI 10.1007/s10071-016-0967-4
PG 11
WC Behavioral Sciences; Zoology
SC Behavioral Sciences; Zoology
GA DI8IE
UT WOS:000373743900018
PM 26908005
ER
PT J
AU Kim, HK
Isaacs-Trepanier, C
Elmi, N
Rapoport, SI
Andreazza, AC
AF Kim, Helena K.
Isaacs-Trepanier, Cameron
Elmi, Nika
Rapoport, Stanley I.
Andreazza, Ana C.
TI Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex
by chronic NMDA administration can be partially prevented by lithium
treatment
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE NMDA; Lipid peroxidation; Mitochondria; Excitotoxicity; Lithium
ID ARACHIDONIC-ACID RELEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBELLAR
GRANULE CELLS; OXIDATIVE STRESS; BIPOLAR DISORDER; RECEPTOR ACTIVATION;
COMPLEX-I; NEURODEGENERATIVE DISORDERS; HIPPOCAMPAL-NEURONS; PREFRONTAL
CORTEX
AB Chronic N-methyl-D-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Kim, Helena K.; Isaacs-Trepanier, Cameron; Elmi, Nika; Andreazza, Ana C.] Univ Toronto, Dept Pharmacol, Med Sci Bldg, Toronto, ON M5S 1A8, Canada.
[Kim, Helena K.; Isaacs-Trepanier, Cameron; Elmi, Nika; Andreazza, Ana C.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada.
[Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
[Andreazza, Ana C.] Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada.
RP Andreazza, AC (reprint author), RM4204,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
EM helenakim0913@gmail.com; cameron.isaacs.trepanier@gmail.com;
nikaelmi@gmail.com; sir@mail.nih.gov; ana.andreazza@utoronto.ca
FU National Institute on Aging, NIH; Canadian Institute of Health Research
[CIHR MOP 133439]; Brain and Behavior Research Foundation (NARSAD);
Ontario Mental Health Foundation
FX The work by SIR was entirely supported by the Intramural Program of the
National Institute on Aging, NIH. ACA receives grant funding from
Canadian Institute of Health Research (CIHR MOP 133439) and Brain and
Behavior Research Foundation (NARSAD). HKK was supported by the Ontario
Mental Health Foundation. Funding sources had no involvement in study
design, collection, analysis and interpretation of data, and preparation
of the manuscript.
NR 62
TC 2
Z9 2
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD MAY
PY 2016
VL 76
BP 59
EP 65
DI 10.1016/j.jpsychires.2016.02.001
PG 7
WC Psychiatry
SC Psychiatry
GA DI3QB
UT WOS:000373412400008
PM 26894301
ER
PT J
AU Andrade, LR
Salles, FT
Grati, M
Manor, U
Kachar, B
AF Andrade, Leonardo R.
Salles, Felipe T.
Grati, M'hamed
Manor, Uri
Kachar, Bechara
TI Tectorins crosslink type II collagen fibrils and connect the tectorial
membrane to the spiral limbus
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Extracellular matrix; Electron microscopy; Immunogold-labeling;
Tectorial membrane; Tectorins
ID INNER-EAR; TRAVELING-WAVES; ALPHA-TECTORIN; HEARING IMPAIRMENT; SENSORY
EPITHELIA; DEAFNESS; MUTATIONS; MATRIX; MOUSE
AB All inner ear organs possess extracellular matrix appendices over the sensory epithelia that are crucial for their proper function. The tectorial membrane (TM) is a gelatinous acellular membrane located above the hearing sensory epithelium and is composed mostly of type II collagen, and alpha and beta tectorins. TM molecules self-assemble in the endolymph fluid environment, interacting medially with the spiral limbus and distally with the outer hair cell stereocilia. Here, we used immunogold labeling in freeze-substituted mouse cochleae to assess the fine localization of both tectorins in distinct TM regions. We observed that the TM adheres to the spiral limbus through a dense thin matrix enriched in alpha- and beta-tectorin, both likely bound to the membranes of interdental cells. Freeze-etching images revealed that type II collagen fibrils were crosslinked by short thin filaments (4 +/- 1.5 nm, width), resembling another collagen type protein, or chains of globular elements (15 +/- 3.2 nm, diameter). Gold-particles for both tectorins also localized adjacent to the type II collagen fibrils, suggesting that these globules might be composed essentially of alpha- and beta-tectorins. Finally, the presence of gold-particles at the TM lower side suggests that the outer hair cell stereocilia membrane has a molecular partner to tectorins, probably stereocilin, allowing the physical connection between the TM and the organ of Corti. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Andrade, Leonardo R.; Salles, Felipe T.; Grati, M'hamed; Manor, Uri; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Andrade, Leonardo R.] Univ Fed Rio de Janeiro, Inst Biomed Sci, Lab Biomineralizat, BR-21941902 Rio De Janeiro, RJ, Brazil.
[Salles, Felipe T.] Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, Gainesville, FL 32610 USA.
[Grati, M'hamed] Univ Miami, Miller Sch Med, Dept Otolaryngol, Mol Genet Lab, Miami, FL 33136 USA.
[Manor, Uri] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, NIH, Bethesda, MD 20892 USA.
RP Andrade, LR (reprint author), Univ Fed Rio de Janeiro, Inst Biomed Sci, Lab Biomineralizat, ICB,CCS,Ilha Fundao, Av Carlos Chagas Filho 373,F2-30, BR-21941902 Rio De Janeiro, RJ, Brazil.; Kachar, B (reprint author), NIDCD, Lab Cell Struct & Dynam, NIH, 35A Convent Dr 3D-824, Bethesda, MD 20892 USA.
EM andrade@histo.ufrj.br; kacharb@nidcd.nih.gov
OI Grati, M'hamed/0000-0002-4490-1682; Manor, Uri/0000-0002-9802-1955
FU NIH [Z01-DC000002]
FX We would like to Dr. Ronald Petralia (NIDCD, NIH) for the use of the TEM
and critical reading of the manuscript, and Nicole Thompson (NIDCD) for
the grammar review. Work was supported by NIH intramural research funds
Z01-DC000002. We declare no conflict of interest.
NR 29
TC 0
Z9 0
U1 5
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
EI 1095-8657
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD MAY
PY 2016
VL 194
IS 2
BP 139
EP 146
DI 10.1016/j.jsb.2016.01.006
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI3QS
UT WOS:000373414200001
PM 26806019
ER
PT J
AU Marabini, R
Ludtke, SJ
Murray, SC
Chiu, W
de la Rosa-Trevin, JM
Patwardhan, A
Heymann, JB
Carazo, JM
AF Marabini, Roberto
Ludtke, Steven J.
Murray, Stephen C.
Chiu, Wah
de la Rosa-Trevin, Jose M.
Patwardhan, Ardan
Heymann, J. Bernard
Carazo, Jose M.
TI The Electron Microscopy eXchange (EMX) initiative
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Electron microscopy; Data sharing; Conventions; Standardization
ID COMMUNITY STANDARD; SOFTWARE SUITE; REPRESENTATION; INFORMATION;
BIOLOGY; FORMAT; MODEL
AB Three-dimensional electron microscopy (3DEM) of ice-embedded samples allows the structural analysis of large biological macromolecules close to their native state. Different techniques have been developed during the last forty years to process cryo-electron microscopy (cryo-EM) data. Not surprisingly, success in analysis and interpretation is highly correlated with the continuous development of image processing packages. The field has matured to the point where further progress in data and methods sharing depends on an agreement between the packages on how to describe common image processing tasks. Such standardization will facilitate the use of software as well as seamless collaboration, allowing the sharing of rich information between different platforms. Our aim here is to describe the Electron Microscopy eXchange (EMX) initiative, launched at the 2012 Instruct Image Processing Center Developer Workshop, with the intention of developing a first set of standard conventions for the interchange of information for single-particle analysis (EMX version 1.0). These conventions cover the specification of the metadata for micrograph and particle images, including contrast transfer function (CTF) parameters and particle orientations. EMX v1.0 has already been implemented in the Bsoft, EMAN, Xmipp and Scipion image processing packages. It has been and will be used in the CTF and EMDataBank Validation Challenges respectively. It is also being used in EMPIAR, the Electron Microscopy Pilot Image Archive, which stores raw image data related to the 3DEM reconstructions in EMDB. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Marabini, Roberto] Univ Autonoma Madrid, Escuela Politecn Super, Campus Univ Autonoma, E-28049 Madrid, Spain.
[Ludtke, Steven J.; Chiu, Wah] Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[de la Rosa-Trevin, Jose M.; Carazo, Jose M.] Natl Ctr Biotechnol CSIC, Biocomp Unit, C Darwin 3,Campus Univ Autonoma, Madrid 28049, Spain.
[Patwardhan, Ardan] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge, England.
[Heymann, J. Bernard] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Murray, Stephen C.] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
RP Marabini, R (reprint author), Univ Autonoma Madrid, Escuela Politecn Super, Campus Univ Autonoma, E-28049 Madrid, Spain.
EM roberto@cnb.csic.es
OI Patwardhan, Ardan/0000-0001-7663-9028; Marabini,
Roberto/0000-0001-7876-1684
FU Spanish Ministry of Economy and Competitiveness [AIC-A-2011-0638,
BIO2013-44647-R, BFU2013-41249-P]; Comunidad de Madrid through grant CAM
[S2010/BMD-2305]; European Union (EU) and Horizon 2020 [EINFRA-2014-2,
654142, EINFRA-2015-1, 675858]; USA National Institutes of Health
[R01GM079429, R01GM080139, P41GM103832]; Instruct, a component of the
European Strategy Forum on Research Infrastructures (ESFRI); Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health
FX The authors acknowledge financial support from the Spanish Ministry of
Economy and Competitiveness through grants AIC-A-2011-0638,
BIO2013-44647-R and BFU2013-41249-P; the Comunidad de Madrid through
grant CAM (S2010/BMD-2305); the European Union (EU) and Horizon 2020
through grants: EINFRA-2014-2: EGI Engage (Proposal: 654142) and
EINFRA-2015-1: West-Life (Proposal: 675858); and the USA National
Institutes of Health through grants: R01GM079429, R01GM080139 and
P41GM103832.; This work was partially funded by Instruct, a component of
the European Strategy Forum on Research Infrastructures (ESFRI), and
supported by national member subscriptions and by the Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health.
NR 29
TC 3
Z9 3
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
EI 1095-8657
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD MAY
PY 2016
VL 194
IS 2
BP 156
EP 163
DI 10.1016/j.jsb.2016.02.008
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI3QS
UT WOS:000373414200003
PM 26873784
ER
PT J
AU Turkbey, B
Choyke, PL
Pinto, PA
AF Turkbey, Baris
Choyke, Peter L.
Pinto, Peter A.
TI Untitled
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Choyke, Peter L.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD MAY
PY 2016
VL 195
IS 5
BP 1427
EP 1427
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA DJ3ZI
UT WOS:000374144800036
PM 26921011
ER
PT J
AU Muniz, JA
Gomez, G
Gonzalez, B
Rivero-Echeto, MC
Cadet, JL
Garcia-Rill, E
Urbano, FJ
Bisagno, V
AF Muniz, Javier A.
Gomez, Gimena
Gonzalez, Betina
Celeste Rivero-Echeto, Maria
Cadet, Jean Lud
Garcia-Rill, Edgar
Urbano, Francisco J.
Bisagno, Veronica
TI Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the
Mouse Striatum
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Cocaine; Caffeine; Striatum; Locomotor; sensitization; Dopamine;
Astroglia
ID ADENOSINE A(2A) RECEPTORS; FIBRILLARY ACIDIC PROTEIN; SUBSTANCE USE
DISORDERS; GENE-EXPRESSION; ORAL CAFFEINE; SENSITIZATION; DOPAMINE;
BRAIN; MECHANISMS; ADDICTION
AB Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 x 5 mg/kg), cocaine (3 x 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.
C1 [Muniz, Javier A.; Gomez, Gimena; Gonzalez, Betina; Bisagno, Veronica] Univ Buenos Aires, CONICET, Inst Invest Farmacol, Buenos Aires, DF, Argentina.
[Celeste Rivero-Echeto, Maria; Urbano, Francisco J.] Univ Buenos Aires, CONICET, Dept Fisiol Biol Mol & Celular Dr Hector Maldonad, Lab Fisiol & Biol Mol,Inst Fisiol Biol Mol & Neur, Junin 956,Piso 5,C1113, Buenos Aires, DF, Argentina.
[Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD USA.
[Garcia-Rill, Edgar] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Ctr Translat Neurosci, Little Rock, AR 72205 USA.
RP Bisagno, V (reprint author), Univ Buenos Aires, CONICET, Inst Invest Farmacol, Buenos Aires, DF, Argentina.
EM vbisagno@ffyb.uba.ar
FU FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica Argentina
[BID 1728 OC.AR. T 2012-0924, BID 1728 OC.AR. PICT2012-1769]; UBACYT
[2014-2017 #201201301013 05BA]; core facilities of Center for
Translational Neuroscience; UAMS, USA; NIH award [P20 GM110702]
FX Dr. Bisagno has been authorized to study drug abuse substances in animal
models by A.N.M.A.T. (National Board of Medicine Food and Medical
Technology, Ministerio de Salud, Argentina). This work was supported by
FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica; BID 1728
OC.AR. T 2012-0924 Argentina (to Dr. Bisagno) and FONCYT-Agencia
Nacional de Promocion Cientifica y Tecnologica; BID 1728 OC.AR.
PICT2012-1769, Argentina, and UBACYT 2014-2017 #201201301013 05BA (to
Dr. Urbano). In addition, this work was supported by core facilities of
the Center for Translational Neuroscience, UAMS, USA, supported by NIH
award P20 GM110702.
NR 69
TC 1
Z9 1
U1 4
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
EI 1476-3524
J9 NEUROTOX RES
JI Neurotox. Res.
PD MAY
PY 2016
VL 29
IS 4
BP 525
EP 538
DI 10.1007/s12640-016-9601-0
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA DI6VM
UT WOS:000373638300007
PM 26858178
ER
PT J
AU Hinkle, SN
Mitchell, EM
Grantz, KL
Ye, AJ
Schisterman, EF
AF Hinkle, Stefanie N.
Mitchell, Emily M.
Grantz, Katherine L.
Ye, Aijun
Schisterman, Enrique F.
TI Maternal Weight Gain During Pregnancy: Comparing Methods to Address Bias
Due to Length of Gestation in Epidemiological Studies
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE Bias; Epidemiology; Weight gain; Pregnancy; Gestational age
ID COLLIDER-STRATIFICATION BIAS; INFANT-MORTALITY; AGE; MODELS; ADJUST
AB BackgroundStudies examining total gestational weight gain (GWG) and outcomes associated with gestational age (GA) are potentially biased. The z-score has been proposed to mitigate this bias. We evaluated a regression-based adjustment for GA to remove the correlation between GWG and GA, and compared it to published weight-gain-for-gestational-age z-scores when applied to a study sample with different underlying population characteristics.
MethodsUsing 65 643 singleton deliveries to normal weight women at 12 US clinical sites, we simulated a null association between GWG and neonatal mortality. Logistic regression was used to estimate approximate relative risks (RR) of neonatal mortality associated with GWG, unadjusted and adjusted for GA, and the z-score, overall and within study sites. Average RRs across 5000 replicates were calculated with 95% coverage probability to indicate model bias and precision, where 95% is nominal.
ResultsUnder a simulated null association, total GWG resulted in a biased mortality estimate (RR = 0.87; coverage = 0%); estimates adjusted for GA were unbiased (RR = 1.00; coverage = 94%). Quintile-specific RRs ranged from 0.97-1.03. Similar results were observed for site-specific analyses. The overall z-score RR was 0.97 (84% coverage) with quintile-specific RRs ranging from 0.64-0.90. Estimates were close to 1.0 at most sites, with coverage from 70-94%. Sites 1 and 6 were biased with RRs of 0.66 and 1.43, respectively, and coverage of 70% and 80%.
ConclusionsAdjusting for GA achieves unbiased estimates of the association between total GWG and neonatal mortality, providing an accessible alternative to the weight-gain-for-gestational-age z-scores without requiring assumptions concerning underlying population characteristics.
C1 [Hinkle, Stefanie N.; Mitchell, Emily M.; Grantz, Katherine L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Ye, Aijun] Glotech Inc, Rockville, MD USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
OI Hinkle, Stefanie/0000-0003-4312-708X; Schisterman,
Enrique/0000-0003-3757-641X; Grantz, Katherine/0000-0003-0276-8534
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200603425C]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (contract number
HHSN267200603425C). The authors would like to thank Drs. Nansi S.
Boghossian, Jennifer A. Hutcheon, Robert W. Platt and Lindsey A. Sjaarda
for their helpful suggestions to earlier versions of the manuscript. The
authors have no conflicts of interest.
NR 19
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAY
PY 2016
VL 30
IS 3
BP 294
EP 304
DI 10.1111/ppe.12284
PG 11
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA DI6QD
UT WOS:000373623800010
PM 26916673
ER
PT J
AU Tian, Q
Resnick, SM
Landman, BA
Huo, YK
Venkatraman, VK
Gonzalez, CE
Simonsick, EM
Shardell, MD
Ferrucci, L
Studenski, SA
AF Tian, Qu
Resnick, Susan M.
Landman, Bennett A.
Huo, Yuankai
Venkatraman, Vijay K.
Gonzalez, Christopher E.
Simonsick, Eleanor M.
Shardell, Michelle D.
Ferrucci, Luigi
Studenski, Stephanie A.
TI Lower gray matter integrity is associated with greater lap time
variation in high-functioning older adults
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Gray matter integrity; Diffusion tensor imaging; Mean diffusivity; Lap
time variation; High-functioning older adults
ID GAIT VARIABILITY; ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; COGNITIVE
DECLINE; BRAIN; RISK; VOLUME; WALKING; PEOPLE
AB Background: Lower integrity of cerebral gray matter is associated with higher gait variability. It is not known whether gray matter integrity is associated with higher lap time variation (LTV), a clinically accessible measure of gait variability, high levels of which have been associated with mortality. This study examines the cross-sectional association between gray matter mean diffusivity (MD) and LTV in community-dwelling older adults.
Methods: Study participants consisted of 449 high-functioning adults aged 50 and older (56.8% female) in the Baltimore Longitudinal Study of Aging, free of overt neurological disease. The magnitude of MD in the gray matter, a measure of impaired tissue integrity, was assessed by diffusion tensor imaging in 16 regions of interest (ROIs) involved with executive function, sensorimotor function, and memory. LTV was assessed as variability in lap time based on individual trajectories over ten 40-m laps. Age, sex, height, and weight were covariates. The model additionally adjusted for mean lap time and health conditions that may affect LTV.
Results: Higher levels of average MD across 16 ROIs were significantly associated with higher LTV after adjustment for covariates. Specifically, higher MD in the precuneus and the anterior and middle cingulate cortices was strongly associated with higher LTV, as compared to other ROIs. The association persisted after adjustment for mean lap time, hypertension, and diabetes.
Conclusions: Lower gray matter integrity in selected areas may underlie greater LTV in high-functioning community-dwelling older adults. Longitudinal studies are warranted to examine whether changes in gray matter integrity precede more variable gait. Published by Elsevier Inc.
C1 [Tian, Qu; Simonsick, Eleanor M.; Shardell, Michelle D.; Ferrucci, Luigi; Studenski, Stephanie A.] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Resnick, Susan M.; Venkatraman, Vijay K.; Gonzalez, Christopher E.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Landman, Bennett A.; Huo, Yuankai] Vanderbilt Univ, Sch Engn, Nashville, TN 37212 USA.
RP Tian, Q (reprint author), NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.; Tian, Q (reprint author), 251 Bayview Blvd,Suite 100,Rm 04B316, Baltimore, MD 21224 USA.
EM qu.tian@nih.gov
RI Tian, Qu/E-5266-2015
OI Tian, Qu/0000-0003-2706-1439
FU National Institute on Aging [03-AG-0325]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging (grant number: 03-AG-0325). The authors
would like to acknowledge the editorial assistance from the National
Institutes of Health Fellows Editorial Board.
NR 35
TC 1
Z9 1
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
EI 1873-6815
J9 EXP GERONTOL
JI Exp. Gerontol.
PD MAY
PY 2016
VL 77
BP 46
EP 51
DI 10.1016/j.exger.2016.02.009
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA DH5GZ
UT WOS:000372815800007
PM 26899565
ER
PT J
AU O'Suoji, C
Welch, JJG
Perkins, SL
Smith, LM
Weitzman, S
Simko, SJ
Galardy, PJ
Bollard, CM
Gross, TG
Termuhlen, AM
AF O'Suoji, Chibuzo
Welch, Jennifer J. G.
Perkins, Sherrie L.
Smith, Lynette M.
Weitzman, Sheila
Simko, Stephen J.
Galardy, Paul J.
Bollard, Catherine M.
Gross, Thomas G.
Termuhlen, Amanda M.
TI Rare Pediatric Non-Hodgkin Lymphomas: A Report From Children's Oncology
Group Study ANHL 04B1
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE cutaneous lymphoma; follicular lymphoma; Non-Hodgkin lymphoma
ID T-CELL LYMPHOMA; FOLLICULAR-LYMPHOMA; CLINICOPATHOLOGICAL FEATURES;
CUTANEOUS LYMPHOMA; MYCOSIS-FUNGOIDES; YOUNG-ADULTS; EXPERIENCE;
CHILDHOOD; TRANSPLANTATION; THERAPY
AB BackgroundNon-Hodgkin lymphoma (NHL) is a relatively common malignancy in pediatric patients; however, a small subgroup have unusual lymphoma subtypes for the pediatric population.
ProcedureThe Children's Oncology Group Rare and Cutaneous NHL registry's (protocol ANHL 04B1) main objectives were to determine the pathologic, biologic, and clinical features of rare and cutaneous pediatric NHL and establish a bank of centrally reviewed tissue specimens. We report the clinical data, treatment data, and outcome for rare pediatric NHL.
ResultsIn 101 lymphomas, there is a 97.8% concordance between the reviewing study pathologists and an 87.6% concordance between the central and institutional pathology review. Samples in the specimen bank include primary tumor tissue that is snap frozen, in paraffin blocks, or H&E-stained and unstained paraffin slides as well as blood, serum, and bone marrow. This descriptive analysis shows that children with pediatric follicular lymphoma, mucosa-associated lymphoid tissue, nodal marginal zone lymphoma, primary cutaneous, primary central nervous system lymphoma, and subcutaneous panniculitis-like T-cell lymphomas have 100% survival at a median of 2 years from enrollment. There are early deaths, mostly from progressive disease, in subjects with peripheral T-cell (not otherwise specified), NKT, and hepatosplenic T-cell lymphomas.
ConclusionsThis registry provides high-quality biologic specimens with clinical data to investigators working on the biology of these unusual pediatric diseases.
C1 [O'Suoji, Chibuzo] W Virginia Univ, Div Pediat Hematol Oncol, Charleston, WV 25304 USA.
[Welch, Jennifer J. G.] Brown Univ, Hasbro Childrens Hosp, Alpert Med Sch, Div Pediat Hematol Oncol, Providence, RI 02912 USA.
[Perkins, Sherrie L.] Univ Utah Hlth Sci, Dept Pathol, Salt Lake City, UT USA.
[Smith, Lynette M.] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE USA.
[Weitzman, Sheila] Hosp Sick Children, Div Pediat Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Simko, Stephen J.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Galardy, Paul J.] Mayo Clin, Div Pediat Hematol Oncol, Rochester, MN USA.
[Bollard, Catherine M.] George Washington Univ, Childrens Natl Hlth Syst, Washington, DC USA.
[Gross, Thomas G.] NCI, Rockville, MD USA.
[Termuhlen, Amanda M.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA.
RP Termuhlen, AM (reprint author), Childrens Hosp Los Angeles, Div Pediat Hematol Oncol BMT, 4650 Sunset Blvd,Mailstop 54, Los Angeles, CA 90027 USA.
EM atermuhlen@chla.usc.edu
FU COG [U10CA098543]; Human Specimen Banking in NCI [U24CA114766];
Statistics Data Center [U10CA098413]
FX Grant sponsor: COG Chair's; Grant number: U10CA098543; Grant sponsor:
Human Specimen Banking in NCI-Sponsored Clinical Trials; Grant number:
U24CA114766; Grant sponsor: Statistics & Data Center; Grant number:
U10CA098413.
NR 38
TC 4
Z9 4
U1 4
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2016
VL 63
IS 5
BP 794
EP 800
DI 10.1002/pbc.25881
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DH7CD
UT WOS:000372947900005
PM 26728447
ER
PT J
AU Smarr, MM
Grantz, KL
Zhang, CL
Sundaram, R
Maisog, JM
Barr, DB
Louis, GMB
AF Smarr, Melissa M.
Grantz, Katherine L.
Zhang, Cuilin
Sundaram, Rajeshwari
Maisog, Jose M.
Barr, Dana Boyd
Louis, Germaine M. Buck
TI Persistent organic pollutants and pregnancy complications
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Gestational diabetes mellitus; Hypertension; Organochlorine pesticides;
Polybrominated diphenyl ethers; Preconception
ID GESTATIONAL DIABETES-MELLITUS; POLYBROMINATED DIPHENYL ETHERS; SERUM
CONCENTRATIONS; HYPERTENSIVE DISORDERS; GLUCOSE-METABOLISM; DETECTION
LIMITS; EXPOSURE; HEALTH; ASSOCIATION; POPULATION
AB We sought to investigate the relationship between maternal preconception exposures to persistent organic pollutants (POPs) and pregnancy complications, gestational diabetes (GDM) and gestational hypertension. Data from 258 (51%) women with human chorionic gonadotropin (hCG) confirmed pregnancies reaching >= 24 weeks gestation, from a prospective cohort of 501 couples who discontinued contraception to attempt pregnancy, were analyzed. Preconception concentrations of 9 organochlorine pesticides (OCPs) and 10 polybrominated diphenyl ethers (PBDEs) were quantified in serum. In separate multiple logistic regression models of self-reported physician diagnosed outcomes: GDM (11%) and gestational hypertension (10%), chemicals were natural log-transformed and rescaled by their standard deviation (SD). Models were adjusted for serum lipids, and then adjusted for age, body mass index, race, and smoking. Models were additionally adjusted for the sum of the remaining POPs in each chemical class. Women's serum concentration of PBDE congener 153 (PBDE-153) was positively associated with an increased odds of GDM per SD increase in log-transformed concentration, for unadjusted (OR = 1.36, 95% CI: 1.02-1.81), a priori adjusted (OR = 1.38, 95% CI: 1.03-1.86) and with the sum of remaining PBDEs (OR = 1.79, 95% CI: 1.18, 2.74) models. Our findings suggest that at environmentally relevant concentrations, maternal exposure to POPs prior to conception may contribute to increased chance of developing GDM. Published by Elsevier B.V.
C1 [Smarr, Melissa M.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
[Grantz, Katherine L.; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
[Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
[Maisog, Jose M.] Glotech Inc, Rockville, MD 20852 USA.
[Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, 1518 Clifton Rd, Atlanta, GA 30322 USA.
RP Smarr, MM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA.
EM melissa.smarr@mail.nih.gov; katherine.grantz@nih.gov;
zhangcu@mail.nih.gov; sundaramr2@mail.nih.gov; bravas02@gmail.com;
dbbarr@emory.edu; louisg@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490; Sundaram,
Rajeshwari/0000-0002-6918-5002; Grantz, Katherine/0000-0003-0276-8534
FU NICHD [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358]
FX This research was supported by the Intramural Research Program of the
NICHD (contracts N01-HD-3-3355, N01-HD-3-3356, and NOH-HD-3-3358).
NR 46
TC 5
Z9 5
U1 6
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
EI 1879-1026
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD MAY 1
PY 2016
VL 551
BP 285
EP 291
DI 10.1016/j.scitotenv.2016.02.030
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DH2BT
UT WOS:000372589800031
PM 26878640
ER
PT J
AU Poniewierska-Baran, A
Schneider, G
Sun, WY
Abdelbaset-Ismail, A
Barr, FG
Ratajczak, MZ
AF Poniewierska-Baran, Agata
Schneider, Gabriela
Sun, Wenyue
Abdelbaset-Ismail, Ahmed
Barr, Frederic G.
Ratajczak, Mariusz Z.
TI Human rhabdomyosarcoma cells express functional pituitary and gonadal
sex hormone receptors: therapeutic implications
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE rhabdomyosarcoma; follicle-stimulating hormone; luteinizing hormone;
androgen; proliferation; metastasis
ID TISSUE-LEVELS INCREASE; ALVEOLAR RHABDOMYOSARCOMA;
HEPATOCELLULAR-CARCINOMA; PROMETASTATIC FACTORS; ESTROGEN-RECEPTORS;
INHIBITORY FACTOR; BIOACTIVE LIPIDS; TUMOR-METASTASIS; GASTRIC-CANCER;
LUNG-CANCER
AB Evidence has accumulated that sex hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of sex hormone receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal sex hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that sex hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS.
C1 [Poniewierska-Baran, Agata; Schneider, Gabriela; Abdelbaset-Ismail, Ahmed; Ratajczak, Mariusz Z.] Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, 500 S Floyd St,Room 107, Louisville, KY 40202 USA.
[Poniewierska-Baran, Agata] Pomeranian Med Univ, Dept Physiol, Szczecin, Poland.
[Sun, Wenyue; Ratajczak, Mariusz Z.] Med Univ Warsaw, Dept Regenerat Med, Warsaw, Poland.
[Barr, Frederic G.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
RP Ratajczak, MZ (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, 500 S Floyd St,Room 107, Louisville, KY 40202 USA.
EM mzrata01@louisville.edu
RI Abdelbaset Ismail , Ahmed/P-4700-2015
OI Abdelbaset Ismail , Ahmed/0000-0002-2135-1753
FU NIH [2R01 DK074720, R01HL112788]; Stella and Henry Endowment; Maestro
grant [2011/02/A/NZ4/00035]; NCN Harmonia Grant
[UMO-2014/14/M/NZ3/00475]; Intramural Research Program of the National
Cancer Institute
FX We would like to thank Dr Sylwia Rzeszotek from Pomeranian Medical
University for her help with immunofluorescence staining. The present
study was supported by the NIH grants 2R01 DK074720 and R01HL112788, the
Stella and Henry Endowment, the Maestro grant 2011/02/A/NZ4/00035 and
the NCN Harmonia Grant UMO-2014/14/M/NZ3/00475 to M.Z.R. The work by
F.G.B. and W.S. was supported by the Intramural Research Program of the
National Cancer Institute.
NR 55
TC 1
Z9 1
U1 0
U2 5
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAY
PY 2016
VL 48
IS 5
BP 1815
EP 1824
DI 10.3892/ijo.2016.3439
PG 10
WC Oncology
SC Oncology
GA DH1TU
UT WOS:000372568600006
PM 26983595
ER
PT J
AU Al-Dimasi, S
Saloum, G
Saykali, B
Khoury, O
Liu, SH
Lepla, SH
Abi-Habib, R
El-Sibai, M
AF Al-Dimasi, Saleh
Saloum, Gilbert
Saykali, Bechara
Khoury, Oula
Liu, Shihui
Lepla, Stephen H.
Abi-Habib, Ralph
El-Sibai, Mirvat
TI Targeting the MAP kinase pathway in astrocytoma cells using a
recombinant anthrax lethal toxin as a way to inhibit cell motility and
invasion
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE anthrax toxin; astrocytomas; motility; invasion; MAPK; RhoA
ID RHO-GTPASES; SIGNALING PATHWAYS; IN-VIVO; CANCER; MIGRATION; RECEPTOR;
TUMORS; ROLES; INACTIVATION; ACTIVATION
AB Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor.
C1 [Al-Dimasi, Saleh; Saloum, Gilbert; Saykali, Bechara; Khoury, Oula; Abi-Habib, Ralph; El-Sibai, Mirvat] Lebanese Amer Univ, Dept Nat Sci, POB 13-5053, Beirut 11022801, Lebanon.
[Liu, Shihui; Lepla, Stephen H.] NIH, Microbial Pathogenesis Sect, Parasit Dis Lab, Bldg 10, Bethesda, MD 20892 USA.
RP El-Sibai, M (reprint author), Lebanese Amer Univ, Dept Nat Sci, POB 13-5053, Beirut 11022801, Lebanon.
EM mirvat.elsibai@lau.edu.lb
FU Natural Science Department at Lebanese American University; [CA100324];
[GM064346]
FX The ROI_Tracker software was supplied by David Entenberg and John
Condeelis as supported by CA100324 and GM064346. The present study was
supported by the Natural Science Department at the Lebanese American
University.
NR 37
TC 0
Z9 0
U1 1
U2 7
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAY
PY 2016
VL 48
IS 5
BP 1913
EP 1920
DI 10.3892/ijo.2016.3431
PG 8
WC Oncology
SC Oncology
GA DH1TU
UT WOS:000372568600016
PM 26984023
ER
PT J
AU Ruan, XB
AF Ruan, Xiangbo
TI Long Non-Coding RNA Central of Glucose Homeostasis
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE LncRNA; GLUCOSE METABOLISM; DIABETES; CANCER METABOLISM
ID BETA-CELL TRANSCRIPTOME; PROSTATE-SPECIFIC GENE; CANCER METASTASIS;
BLADDER-CARCINOMA; METABOLISM; EXPRESSION; DIFFERENTIATION;
PROLIFERATION; UCA1; SRA
AB Glucose metabolism is one of the fundamental biochemical processes in mammals. Metabolism of glucose is subjected to tissue and cell specific regulation involving many transporters, enzymes, and transcriptional factors. Dysregulation of glucose metabolism has been linked to many human diseases such as diabetes and cancer. Long non-coding RNAs (lncRNAs) are a novel class of functional RNAs that regulate multiple biological functions through diverse mechanisms including recruitment of epigenetic modifier proteins, control of mRNA decay and translation, and DNA sequestration of transcription factors. Recent studies have demonstrated that lncRNAs play an important role in regulating differentiation and homeostasis of metabolic tissues. This review will discuss lncRNA biology with a focus on their role in regulating glucose metabolism in cancer cells and metabolic tissues. (C) 2015 Wiley Periodicals, Inc.
C1 [Ruan, Xiangbo] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Ruan, XB (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM xiangbo.ruan@nih.gov
RI Ruan, Xiangbo/P-9265-2016
NR 57
TC 4
Z9 4
U1 2
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD MAY
PY 2016
VL 117
IS 5
BP 1061
EP 1065
DI 10.1002/jcb.25427
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG7QE
UT WOS:000372278000001
PM 26530464
ER
PT J
AU Winchester, DA
Gurel, B
Till, C
Goodman, PJ
Tangen, CM
Santella, RM
Johnson-Pais, TL
Leach, RJ
Thompson, IM
Xu, JF
Zheng, SL
Lucia, MS
Lippman, SM
Parnes, HL
Isaacs, WB
Drake, CG
De Marzo, AM
Platz, EA
AF Winchester, Danyelle A.
Gurel, Bora
Till, Cathee
Goodman, Phyllis J.
Tangen, Catherine M.
Santella, Regina M.
Johnson-Pais, Teresa L.
Leach, Robin J.
Thompson, Ian M.
Xu, Jianfeng
Zheng, S. Lilly
Lucia, M. Scott
Lippman, Scott M.
Parnes, Howard L.
Isaacs, William B.
Drake, Charles G.
De Marzo, Angelo M.
Platz, Elizabeth A.
TI Key genes involved in the immune response are generally not associated
with intraprostatic inflammation in men without a prostate cancer
diagnosis: Results from the prostate cancer prevention trial
SO PROSTATE
LA English
DT Article
DE genes; inflammation; prostate cancer
ID PLACEBO ARM; RISK; POLYMORPHISM
AB BACKGROUNDWe previously reported that both intraprostatic inflammation and SNPs in genes involved in the immune response are associated with prostate cancer risk and disease grade. In the present study, we evaluated the association between these SNPs and intraprostatic inflammation in men without a prostate cancer diagnosis.
METHODSIncluded in this cross-sectional study were 205 white controls from a case-control study nested in the placebo arm of the Prostate Cancer Prevention Trial. We analyzed inflammation data from the review of H&E-stained prostate tissue sections from biopsies performed per protocol at the end of the trial irrespective of clinical indication, and data for 16 SNPs in key genes involved in the immune response (IL1, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, TNFA; 7 tagSNPs in IL10). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between carrying at least one minor allele and having at least one biopsy core (of a mean of three reviewed) with inflammation.
RESULTSNone of the SNPs evaluated was statistically significantly associated with having at least one core with inflammation. However, possible inverse associations were present for carrying the minor allele of rs2069762 (G) in IL2 (OR=0.51, 95%CI 0.25-1.02); carrying two copies of the minor allele of rs1800871 (T) of IL10 (OR=0.29, 95%CI 0.08-1.00); and carrying the minor allele of rs486907 (A) in RNASEL (OR=0.52, 95%CI 0.26-1.06). After creating a genetic risk score from the three SNPs possibly associated with inflammation, the odds of inflammation increased with increasing number of risk alleles (P-trend=0.008).
CONCLUSIONWhile our findings do not generally support a cross-sectional link between individual SNPs in key genes involved in the immune response and intraprostatic inflammation in men without a prostate cancer diagnosis, they do suggest that some of these variants when in combination may be associated with intraprostatic inflammation in benign tissue. Prostate 76:565-574, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Winchester, Danyelle A.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
[Gurel, Bora; De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Gurel, Bora] Kocaeli Univ, Sch Med, Dept Pathol, Kocaeli, Turkey.
[Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
[Johnson-Pais, Teresa L.; Leach, Robin J.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Xu, Jianfeng; Zheng, S. Lilly] NorthShore Univ Hlth Syst, Program Personalized Canc Care, Evanston, IL USA.
[Xu, Jianfeng; Zheng, S. Lilly] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA.
[Zheng, S. Lilly] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Lucia, M. Scott] Univ Colorado, Dept Pathol, Anschutz Med Campus, Aurora, CO USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Parnes, Howard L.] NCI, Div Canc Prevent, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Isaacs, William B.; Drake, Charles G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA.
[Isaacs, William B.; Drake, Charles G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA.
[Isaacs, William B.; Drake, Charles G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD USA.
RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM eplatz1@jhu.edu
FU National Cancer Institute, National Institutes of Health [P01 CA108964,
P30 CA54174, U10 CA37429, UM1 CA182883, T32 CA009314]
FX Grant sponsor: National Cancer Institute, National Institutes of Health;
Grant numbers: P01 CA108964; P30 CA54174; U10 CA37429; UM1 CA182883; T32
CA009314.
NR 18
TC 1
Z9 1
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2016
VL 76
IS 6
BP 565
EP 574
DI 10.1002/pros.23147
PG 10
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA DH2UW
UT WOS:000372643200005
PM 26771888
ER
PT J
AU Caruso, V
Sreedharan, S
Carlini, VP
Jacobsson, JA
Haitina, T
Hammer, J
Stephansson, O
Crona, F
Sommer, WH
Riserus, U
Lannfelt, L
Marcus, C
Heilig, M
de Barioglio, SR
Fredriksson, R
Schioth, HB
AF Caruso, Vanni
Sreedharan, Smitha
Carlini, Valeria P.
Jacobsson, Josefin A.
Haitina, Tatjana
Hammer, Joanna
Stephansson, Olga
Crona, Filip
Sommer, Wolfgang H.
Riserus, Ulf
Lannfelt, Lars
Marcus, Claude
Heilig, Markus
de Barioglio, Susana R.
Fredriksson, Robert
Schioth, Helgi B.
TI mRNA GPR162 changes are associated with decreased food intake in rat,
and its human genetic variants with impairments in glucose homeostasis
in two Swedish cohorts
SO GENE
LA English
DT Article
DE GPCRs; GPR162; Food intake; Obesity; Glucose homeostasis
ID PROTEIN-COUPLED RECEPTORS; ARCUATE NUCLEUS; EVOLUTIONARY HISTORY; POMC
NEURONS; HUMAN GENOME; BODY-WEIGHT; LEPTIN; BRAIN; EXPRESSION;
RESISTANCE
AB G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized.
Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding.
In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis. (C) 2016 Published by Elsevier B.V.
C1 [Caruso, Vanni; Sreedharan, Smitha; Carlini, Valeria P.; Jacobsson, Josefin A.; Haitina, Tatjana; Hammer, Joanna; Stephansson, Olga; Crona, Filip; Fredriksson, Robert; Schioth, Helgi B.] Uppsala Univ BMC, Unit Funct Pharmacol, Dept Neurosci, SE-75124 Uppsala, Sweden.
[Caruso, Vanni] Univ Tasmania UTAS, Fac Pharm, Hobart, Tas 7001, Australia.
[Carlini, Valeria P.; de Barioglio, Susana R.] Univ Nacl Cordoba, Fac Ciencias Quim Haya Torre & Medina Allende, Dept Farmacol, Ciudad Univ, RA-5016 Cordoba, Argentina.
[Sommer, Wolfgang H.] Cent Inst Mental Hlth, Dept Psychopharmacol, Mannheim, Germany.
[Riserus, Ulf] Uppsala Univ, Dept Publ Hlth & Caring Sci Clin Nutr & Metab, Uppsala, Sweden.
[Lannfelt, Lars] Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Uppsala, Sweden.
[Marcus, Claude] Karolinska Inst, Dept Clin Sci Intervent & Technol, Natl Childhood Obes Ctr, Div Pediat, Stockholm, Sweden.
[Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Caruso, V (reprint author), Biomed Ctr, Dept Neurosci, Unit Funct Pharmacol, Box 593, SE-75124 Uppsala, Sweden.
EM vanni.caruso@neuro.uu.se
FU Swedish Research Council; Ahlens Foundation; Swedish Brain Research
Foundation; Novo Nordisk Foundation; Engkvist Foundation; Magnus
Bergvall Foundation
FX This study was supported by the Swedish Research Council, Ahlens
Foundation, The Swedish Brain Research Foundation, The Novo Nordisk
Foundation, Engkvist Foundation, and Magnus Bergvall Foundation.
NR 42
TC 0
Z9 0
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
EI 1879-0038
J9 GENE
JI Gene
PD MAY 1
PY 2016
VL 581
IS 2
BP 139
EP 145
DI 10.1016/j.gene.2016.01.044
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA DG3DG
UT WOS:000371949100005
PM 26827797
ER
PT J
AU Chandrasekaran, AR
Pushpanathan, M
Halvorsen, K
AF Chandrasekaran, Arun Richard
Pushpanathan, Muthuirulan
Halvorsen, Ken
TI Evolution of DNA origami scaffolds
SO MATERIALS LETTERS
LA English
DT Article
DE DNA origami; DNA scaffolds; DNA self-assembly; DNA-based nanomaterials;
Genome tailoring; DNA nanostructures
ID POLYMERASE-CHAIN-REACTION; FOLDING DNA; PARANEMIC COHESION; NANOSCALE
SHAPES; CRYSTALS; NANOSTRUCTURES; LINKAGE; DESIGN; ARRAYS; TILES
AB Nanoscale materials made using DNA have been increasingly used for applications ranging from bio-sensors to nanoelectronics. Specifically, DNA origami - where one long single-stranded DNA scaffold is folded into nanoscale shapes and structures using short 'staple' oligonucleotides - typically relies on a single-stranded DNA scaffold derived from a viral genome. The sizes of structures that are made rely on the length of the scaffold strand; the most frequently used DNA scaffold is the single-stranded 7249-nucleotide circular M13mp18 genome. Modern techniques used in genome tailoring are now widely exploited for the creation of DNA scaffolds of various lengths for use in DNA origami. DNA scaffolds of lengths ranging from similar to 700-nucleotides to similar to 51,000 nucleotides have been prepared using biotechniques such as polymerase chain reaction, a combination of site-directed mutagenesis and site- and ligation independent cloning, and using the molecular toolbox of restriction and ligation enzymes. Such tailor-made DNA scaffolds allow the creation of origami nanostructures of desired sizes. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Chandrasekaran, Arun Richard; Halvorsen, Ken] SUNY Albany, RNA Inst, Albany, NY 12222 USA.
[Pushpanathan, Muthuirulan] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Chandrasekaran, AR; Halvorsen, K (reprint author), SUNY Albany, RNA Inst, Albany, NY 12222 USA.
EM arunrichard@nyu.edu; khalvorsen@albany.edu
OI Pushpanathan, Muthuirulan/0000-0001-6240-3073
NR 46
TC 5
Z9 5
U1 22
U2 73
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-577X
EI 1873-4979
J9 MATER LETT
JI Mater. Lett.
PD MAY 1
PY 2016
VL 170
BP 221
EP 224
DI 10.1016/j.matlet.2016.01.161
PG 4
WC Materials Science, Multidisciplinary; Physics, Applied
SC Materials Science; Physics
GA DG0TG
UT WOS:000371778000054
ER
PT J
AU McGlynn, KA
Hagberg, K
Chen, J
Braunlin, M
Graubard, BI
Suneja, N
Jick, S
Sahasrabuddhe, VV
AF McGlynn, Katherine A.
Hagberg, Katrina
Chen, Jie
Braunlin, Megan
Graubard, Barry I.
Suneja, Neha
Jick, Susan
Sahasrabuddhe, Vikrant V.
TI Menopausal hormone therapy use and risk of primary liver cancer in the
clinical practice research datalink
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE liver cancer; menopausal hormone therapy
ID PRACTICE RESEARCH DATABASE; PLACEBO-CONTROLLED TRIAL;
HEPATOCELLULAR-CARCINOMA; REPRODUCTIVE FACTORS; REPLACEMENT THERAPY;
METAANALYSIS; WOMEN; HEPATOCARCINOGENESIS; DISEASE; MICE
AB Primary liver cancer occurs less commonly among women than men in almost all countries. This discrepancy has suggested that hormone levels and/or exogenous hormone use could have an effect on risk, although prior studies have reached inconsistent conclusions. Thus, the current study was conducted to examine the relationship between menopausal hormone therapy (MHT) use and development of liver cancer. A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Controls were matched, at a 4-to-1 ratio, to women diagnosed with primary liver cancer between 1988 and 2011. A second match, based on whether the cases and controls had diabetes, was also conducted. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with liver cancer were estimated using conditional logistic regression adjusted for known risk factors. In the overall match, 339 women with liver cancer were matched to 1318 controls. MHT use was associated with a significantly lower risk of liver cancer (ORadj=0.58, 95%CI=0.37-0.90) especially among users of estrogen-only MHT (ORadj=0.44, 95%CI=0.22-0.88) and among past users (ORadj=0.53, 95%CI=0.32-0.88). Among the matched cases (n=58) and controls (n=232) with diabetes, the odds ratios were similar to the overall analysis (ORadj=0.57, 95%CI=0.09-3.53), but did not attain statistical significance. In the current study, MHT use, especially estrogen-only MHT use, was associated with a significantly lower risk of liver cancer. These results support the need of further investigation into whether hormonal etiologies can explain the variation in liver cancer incidence between men and women.
What's new? Pronounced gender discrepancy in the risk of primary liver cancer suggests that steroid hormone levels or exogenous hormone use are related to risk. In this analysis of data from the Clinical Practice Research Datalink in the United Kingdom, risk of liver cancer was found to be significantly reduced among women on menopausal hormone therapy (MHT). The association was evident particularly among users of estrogen-only MHT. The findings suggest that exogenous hormones protect against liver cancer, a phenomenon inviting further investigation.
C1 [McGlynn, Katherine A.; Chen, Jie; Braunlin, Megan; Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hagberg, Katrina; Suneja, Neha; Jick, Susan] Boston Collaborat Drug Surveillance Program, Lexington, MA USA.
[Hagberg, Katrina; Suneja, Neha; Jick, Susan] Boston Univ, Sch Publ Hlth, Lexington, MA USA.
[Sahasrabuddhe, Vikrant V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM mcglynnk@mail.nih.gov
RI CPRD, CPRD/B-9594-2017
FU National Institutes of Health
FX Grant sponsor: National Institutes of Health
NR 33
TC 1
Z9 1
U1 2
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2016
VL 138
IS 9
BP 2146
EP 2153
DI 10.1002/ijc.29960
PG 8
WC Oncology
SC Oncology
GA DF2GY
UT WOS:000371161800010
PM 26662112
ER
PT J
AU Taunk, P
Hecht, E
Stolzenberg-Solomon, R
AF Taunk, Pulkit
Hecht, Eric
Stolzenberg-Solomon, Rachael
TI Are meat and heme iron intake associated with pancreatic cancer? Results
from the NIH-AARP diet and health cohort
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE pancreatic cancer; heme iron; meat
ID HETEROCYCLIC AMINE CONTENT; GLYCATION END-PRODUCTS; NUTRITIONAL FACTORS;
PROCESSED MEAT; OXIDATIVE STRESS; VARYING DEGREES; FOOD GROUPS; RISK;
POPULATION; RED
AB Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH-AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow-up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self-reported diabetes and energy-adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR=1.20, 95% CI 1.02-1.42, p-trend=0.03), red meat (HR=1.22, 95% CI 1.01-1.48, p-trend=0.02), high-temperature cooked meat (HR=1.21, 95% CI 1.00-1.45, p-trend=0.02), grilled/barbequed meat (HR=1.24, 95% CI 1.03-1.50, p-trend=0.007), well/very well done meat (HR=1.32, 95% CI 1.10-1.58, p-trend=0.005) and heme iron from red meat (Q4 vs. Q1: HR=1.21, 95% CI 1.01-1.45, p-trend=0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR=1.33, 95% CI 1.02-1.74, p-trend=0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk.
What's new? How would you like your steak? A new study examines whether meat cooking techniques boost pancreatic cancer risk. The comprehensive investigation also looked at total meat intake; meat intake by type; as well as heme iron and meat mutagen intake, using data from a questionnaire given to more than 567,000 persons. Of these, 1417 developed pancreatic cancer. Analysis showed that higher risk of pancreatic cancer accompanies total meat consumption, high temperature cooking, grilled meat, well done meat, red meat, and heme iron intake. This is the largest study yet to evaluate the link between meat cooking methods, heme iron, and pancreatic cancer.
C1 [Taunk, Pulkit; Hecht, Eric] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA.
[Taunk, Pulkit; Stolzenberg-Solomon, Rachael] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
RP Stolzenberg-Solomon, R (reprint author), 9609 Med Ctr Dr,Room 6E420, Rockville, MD 20850 USA.; Taunk, P (reprint author), 4050 Presidential Dr, Palm Harbor, FL 34685 USA.
EM pt44@med.miami.edu; rs221z@nih.gov
FU National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services. Cancer incidence data from
Arizona were collected by the Arizona Cancer Registry; from Georgia by
the Georgia Center for Cancer Statistics; from California by the
California Department of Health Services, Cancer Surveillance Section;
from Michigan by the Michigan Cancer Surveillance Program; from Florida
by the Florida Cancer Data System under contract to the Department of
Health; from Louisiana by the Louisiana Tumor Registry; from New Jersey
by the New Jersey State Cancer Registry; from North Carolina by the
North Carolina Central Cancer Registry; from Pennsylvania by the
Division of Health Statistics and Research, Pennsylvania Department of
Health; from Texas by the Texas Cancer Registry and from Nevada by the
Nevada Central Cancer Registry of the Division of Public and Behavioral
Health for the State of Nevada. The views expressed herein are solely
those of the authors and do not necessarily reflect those of the cancer
registries or contractors. The Pennsylvania Department of Health
specifically disclaims responsibility for any analyses, interpretations
or conclusions. The authors are indebted to the participants of the
NIH-AARP Diet and Health Study for their outstanding cooperation.
NR 40
TC 3
Z9 3
U1 4
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2016
VL 138
IS 9
BP 2172
EP 2189
DI 10.1002/ijc.29964
PG 18
WC Oncology
SC Oncology
GA DF2GY
UT WOS:000371161800013
PM 26666579
ER
PT J
AU Minic, D
Pajevic, S
AF Minic, Djordje
Pajevic, Sinisa
TI Emergent "quantum" theory in complex adaptive systems
SO MODERN PHYSICS LETTERS B
LA English
DT Article
DE Emergent quantum theory; complex adaptive systems; system stability;
Lotka-Volterra model
ID LOTKA-VOLTERRA EQUATIONS; HAMILTONIAN STRUCTURES; STATISTICAL DISTANCE;
MECHANICS; MULTISTABILITY; QUANTIZATION; MODELS; STATES; WAVE
AB Motivated by the question of stability, in this paper we argue that an effective quantum-like theory can emerge in complex adaptive systems. In the concrete example of stochastic Lotka-Volterra dynamics, the relevant effective "Planck constant" associated with such emergent "quantum" theory has the dimensions of the square of the unit of time. Such an emergent quantum-like theory has inherently nonclassical stability as well as coherent properties that are not, in principle, endangered by thermal fluctuations and therefore might be of crucial importance in complex adaptive systems.
C1 [Minic, Djordje] Virginia Tech, Dept Phys, Blacksburg, VA 24061 USA.
[Pajevic, Sinisa] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Minic, D (reprint author), Virginia Tech, Dept Phys, Blacksburg, VA 24061 USA.; Pajevic, S (reprint author), NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
EM dminic@vt.edu; pajevic@nih.gov
FU US Department of Energy [DE-FG02-13ER41917]; Intramural Research Program
of the Center for Information Technology, National Institutes of Health
FX We thank V. Balasubramanim N. Goldenfeld, W. Mather, I. Nemenman, M.
Pleimling, ling V. Scarola, U. Tauber arrd J. Xing for illuminating
discussions and comments. D. M. thanks the Aspen Center for Physics for
providing a stimulating environment, for work. DM is supported in part
by the US Department of Energy under contract DE-FG02-13ER41917, task A.
S. Pajevic was supported by the Intramural Research Program of the
Center for Information Technology, National Institutes of Health.
NR 59
TC 0
Z9 0
U1 1
U2 1
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 0217-9849
EI 1793-6640
J9 MOD PHYS LETT B
JI Mod. Phys. Lett. B
PD APR 30
PY 2016
VL 30
IS 11
AR 1650201
DI 10.1142/S0217984916502018
PG 12
WC Physics, Applied; Physics, Condensed Matter; Physics, Mathematical
SC Physics
GA DM1QD
UT WOS:000376120400012
ER
PT J
AU Zatzick, DF
Russo, J
Darnell, D
Chambers, DA
Palinkas, L
Van Eaton, E
Wang, J
Ingraham, LM
Guiney, R
Heagerty, P
Comstock, B
Whiteside, LK
Jurkovich, G
AF Zatzick, Douglas F.
Russo, Joan
Darnell, Doyanne
Chambers, David A.
Palinkas, Lawrence
Van Eaton, Erik
Wang, Jin
Ingraham, Leah M.
Guiney, Roxanne
Heagerty, Patrick
Comstock, Bryan
Whiteside, Lauren K.
Jurkovich, Gregory
TI An effectiveness-implementation hybrid trial study protocol targeting
posttraumatic stress disorder and comorbidity
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Traumatic injury; Multiple chronic conditions; Posttraumatic stress
disorder; Depression; Suicidal ideation; Substance abuse;
Effectiveness-implementation hybrid; Pragmatic clinical trial; American
College of Surgeons; Policy
ID RANDOMIZED CONTROLLED-TRIAL; STEPPED COLLABORATIVE CARE; INJURED TRAUMA
SURVIVORS; POLYTRAUMA-CLINICAL-TRIAD; TIME TRADE-OFF; BRIEF
INTERVENTION; SUBSTANCE USE; PREVENTIVE INTERVENTIONS; FUNCTIONAL
OUTCOMES; DEPRESSIVE SYMPTOMS
AB Background: Each year in the USA, 1.5-2.5 million Americans are so severely injured that they require inpatient hospitalization. Multiple conditions including posttraumatic stress disorder (PTSD), alcohol and drug use problems, depression, and chronic medical conditions are endemic among physical trauma survivors with and without traumatic brain injuries.
Methods/design: The trauma survivors outcomes and support (TSOS) effectiveness-implementation hybrid trial is designed to test the delivery of high-quality screening and intervention for PTSD and comorbidities across 24 US level I trauma center sites. The pragmatic trial aims to recruit 960 patients. The TSOS investigation employs a stepped wedge cluster randomized design in which sites are randomized sequentially to initiate the intervention. Patients identified by a 10-domain electronic health record screen as high risk for PTSD are formally assessed with the PTSD Checklist for study entry. Patients randomized to the intervention condition will receive stepped collaborative care, while patients randomized to the control condition will receive enhanced usual care. The intervention training begins with a 1-day on-site workshop in the collaborative care intervention core elements that include care management, medication, cognitive behavioral therapy, and motivational-interviewing elements targeting PTSD and comorbidity. The training is followed by site supervision from the study team. The investigation aims to determine if intervention patients demonstrate significant reductions in PTSD and depressive symptoms, suicidal ideation, alcohol consumption, and improvements in physical function when compared to control patients. The study uses implementation science conceptual frameworks to evaluate the uptake of the intervention model. At the completion of the pragmatic trial, results will be presented at an American College of Surgeons' policy summit. Twenty-four representative US level I trauma centers have been selected for the study, and the protocol is being rolled out nationally.
Discussion: The TSOS pragmatic trial simultaneously aims to establish the effectiveness of the collaborative care intervention targeting PTSD and comorbidity while also addressing sustainable implementation through American College of Surgeons' regulatory policy. The TSOS effectiveness-implementation hybrid design highlights the importance of partnerships with professional societies that can provide regulatory mandates targeting enhanced health care system sustainability of pragmatic trial results.
C1 [Zatzick, Douglas F.; Russo, Joan; Darnell, Doyanne; Ingraham, Leah M.; Guiney, Roxanne] Univ Washington, Dept Psychiat & Behav Sci, 325 Ninth Ave,Box 359911, Seattle, WA 98104 USA.
[Chambers, David A.] NCI, Div Canc Control & Populat Sci, BG 9609 MSC 9760,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Palinkas, Lawrence] Univ So Calif, Sch Social Work, Montgomery Ross Fisher Bldg,Room 339, Los Angeles, CA 90089 USA.
[Van Eaton, Erik] Univ Washington, Dept Surg, 325 Ninth Ave,Box 359796, Seattle, WA 98104 USA.
[Zatzick, Douglas F.; Wang, Jin] Univ Washington, Harborview Injury Prevent Res Ctr, 325 Ninth Ave,Box 359960, Seattle, WA 98104 USA.
[Heagerty, Patrick; Comstock, Bryan] Univ Washington, Dept Biostat, 1705 NE Pacific St,Box 357232, Seattle, WA 98195 USA.
[Whiteside, Lauren K.] Univ Washington, Div Emergency Med, 25 Ninth Ave,Box 359702, Seattle, WA 98104 USA.
[Jurkovich, Gregory] Univ Calif Davis, Dept Surg, 2221 Stockton Blvd,Cypress 3111, Sacramento, CA 95817 USA.
RP Zatzick, DF (reprint author), Univ Washington, Dept Psychiat & Behav Sci, 325 Ninth Ave,Box 359911, Seattle, WA 98104 USA.; Zatzick, DF (reprint author), Univ Washington, Harborview Injury Prevent Res Ctr, 325 Ninth Ave,Box 359960, Seattle, WA 98104 USA.
EM dzatzick@uw.edu
FU National Institutes of Health (NIH) Common Fund, through Office of
Strategic Coordination within the Office of the NIH Director [U54
AT007748, 1UH2MH106338-01/4UH3MH106338-02]; National Institute of Mental
Health [1 K24MH086814-01A1]
FX This work is supported by the National Institutes of Health (NIH) Common
Fund, through cooperative agreements (U54 AT007748,
1UH2MH106338-01/4UH3MH106338-02) from the Office of Strategic
Coordination within the Office of the NIH Director, and the National
Institute of Mental Health (1 K24MH086814-01A1). The views presented
here are solely the responsibility of the authors and do not necessarily
represent the official views of the National Institutes of Health.
NR 152
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U1 4
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD APR 30
PY 2016
VL 11
AR 58
DI 10.1186/s13012-016-0424-4
PG 16
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DK7MO
UT WOS:000375110000001
PM 27130272
ER
PT J
AU Smallwood, RF
Potter, JS
Robin, DA
AF Smallwood, Rachel F.
Potter, Jennifer S.
Robin, Donald A.
TI Neurophysiological mechanisms in acceptance and commitment therapy in
opioid-addicted patients with chronic pain
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Chronic pain; Opioid addiction; Acceptance and Commitment Therapy
ID INTRINSIC BRAIN CONNECTIVITY; FIBROMYALGIA; METAANALYSIS; MINDFULNESS
AB Acceptance and Commitment Therapy (ACT) has been effectively utilized to treat both chronic pain and substance use disorder independently. Given these results and the vital need to treat the comorbidity of the two disorders, a pilot ACT treatment was implemented in individuals with comorbid chronic pain and opioid addiction. This pilot study supported using neurophysiology to characterize treatment effects and revealed that, following ACT, participants with this comorbidity exhibited reductions in brain activation due to painful stimulus and in connectivity at rest. (c) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Smallwood, Rachel F.; Robin, Donald A.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
[Smallwood, Rachel F.; Potter, Jennifer S.; Robin, Donald A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
RP Smallwood, RF (reprint author), Natl Inst Neurol Disorders & Stroke, 10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA.
EM rachel.smallwood@nih.gov
FU NIH NIDA [K23DA022297-04]
FX This study was supported by NIH NIDA Grant K23DA022297-04 (Potter). The
authors thank Harvir Virk for his contributions.
NR 18
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Z9 0
U1 8
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD APR 30
PY 2016
VL 250
BP 12
EP 14
DI 10.1016/j.pscychresns.2016.03.001
PG 3
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DK8EO
UT WOS:000375160200002
PM 27107155
ER
PT J
AU Danaher, MR
Albert, PS
Roy, A
Schisterman, EF
AF Danaher, Michelle R.
Albert, Paul S.
Roy, Aninyda
Schisterman, Enrique F.
TI Estimation of interaction effects using pooled biospecimens in a
case-control study
SO STATISTICS IN MEDICINE
LA English
DT Article
DE cytokines; expectation maximization; logistic regression; pooling
designs; skewed biomarkers
ID EM ALGORITHM; MISCARRIAGE; EXPOSURE; RISK
AB Pooling, or physically mixing biospecimens, prior to evaluating biomarkers dramatically reduces biomarker evaluation cost, reduces the quantity of biospecimens required of each individual, and may reduce the percentage of laboratory measurements below the lower limit of detection. Motivated by a case-control study on miscarriage (binary outcome) and cytokines (continuous exposures), we are interested in estimating parameters in a logistic regression, where individuals with the same disease status (with or without a miscarriage) are paired and their pooled cytokine concentrations are assessed. Previous research has proposed a set-based logistic model to evaluate the relationship between a disease and pooled exposures. While the set-based logistic model is very useful for estimating main effects, it cannot estimate interactions of continuous exposures when both are measured in pools. Therefore, we propose using the expectation maximization (EM) algorithm to obtain estimators of all parameters in logistic regression model, including interactions effects. Using a simulation study, we present comparisons of efficiency under different scenarios where exposures have been measured in pools and individually. Our simulations show that randomly sampling half of the available biospecimens has less efficiency than pooling pairs of biospecimens stratified by disease status. The EM algorithm provides a method for estimating interaction effects when biospecimens have already been pooled for other reasons such as the gain in efficiency for estimating main effects demonstrated by previous research. This manuscript demonstrates that the EM algorithm offers a promising approach to estimate interaction effects of pooled biospecimens. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Danaher, Michelle R.; Albert, Paul S.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut BLVD Room 7B03H,MSC 7510, Bethesda, MD 20892 USA.
[Danaher, Michelle R.; Roy, Aninyda] Univ Maryland, Dept Math & Stat, Baltimore, MD 21201 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut BLVD Room 7B03H,MSC 7510, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Long-Range Research Initiative of the American Chemistry Council;
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health, Bethesda, MD [HHSN275200403394C, HHSN275201100002I
Task 1 HHSN27500001]
FX This research was supported by the Long-Range Research Initiative of the
American Chemistry Council and the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health, Bethesda, MD
(Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001).
This work utilized the computational resources of the NIH HPC Biowulf
cluster. (http://hpc.nih.gov)
NR 19
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U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD APR 30
PY 2016
VL 35
IS 9
BP 1502
EP 1513
DI 10.1002/sim.6798
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DI8GQ
UT WOS:000373739900007
PM 26553532
ER
PT J
AU Andersson, M
Diao, XX
Wohlfarth, A
Scheidweiler, KB
Huestis, MA
AF Andersson, Maria
Diao, Xingxing
Wohlfarth, Ariane
Scheidweiler, Karl B.
Huestis, Marilyn A.
TI Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by
human hepatocyte and liver microsome incubations and high-resolution
mass spectrometry
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID IN-VITRO; 3-N-BUTYLPHTHALIDE NBP; ACYL GLUCURONIDES; 5-FLUORO ANALOG;
DRUG DISCOVERY; IDENTIFICATION; PHARMACOKINETICS; URINE; DERIVATIVES;
STABILITY
AB RationaleAMB (methyl (1-pentyl-1H-indazole-3-carbonyl)-L-valinate)) and its fluoro analog 5F-AMB (methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate) are two new synthetic cannabinoids that are structural analogs of AB-PINACA and 5F-AB-PINACA, respectively. 5F-AMB is scheduled as an illicit drug in China, Germany, Singapore and Japan, and no metabolism data are currently available for either drug. The aim of the present work was to investigate the metabolism of AMB and 5F-AMB and propose appropriate markers to identify their intake in clinical or forensic cases.
MethodsAMB and 5F-AMB were incubated in human hepatocytes (10 mol/L) to generate phase I and II metabolites, which were identified with a TripleTOF 5600(+) high-resolution mass spectrometer. AMB and 5F-AMB metabolic stability studies also were performed with human liver microsomes (HLM) to evaluate metabolic clearances, and to adequately design the human hepatocyte experiment.
ResultsAMB and 5F-AMB were quickly metabolized in HLM with a 1.1 0.1 and 1.0 +/- 0.2min T-1/2, respectively. The predominant metabolic pathway for AMB and 5F-AMB in hepatocytes was ester hydrolysis, and further oxidation and/or glucuronidation. In total, 19 metabolites were identified for AMB and 17 for 5F-AMB. We describe metabolites to differentiate AMB from 5F-AMB, and metabolites that are common to both analytes due to oxidative defluorination of 5F-AMB.
ConclusionsFor the first time, AMB and 5F-AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA
C1 [Andersson, Maria; Diao, Xingxing; Wohlfarth, Ariane; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, IRP, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
[Wohlfarth, Ariane] Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
[Wohlfarth, Ariane] Linkoping Univ, Dept Drug Res, S-58185 Linkoping, Sweden.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, IRP, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
EM marilyn.huestis@gmail.com
FU Intramural Research Program (IRP) of the National Institute on Drug
Abuse, National Institutes of Health
FX This research was funded by the Intramural Research Program (IRP) of the
National Institute on Drug Abuse, National Institutes of Health. We
would also like to acknowledge the Molecular Discovery Company for
providing the MetaSite software.
NR 36
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U1 6
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-4198
EI 1097-0231
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD APR 30
PY 2016
VL 30
IS 8
BP 1067
EP 1078
DI 10.1002/rcm.7538
PG 12
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA DH8US
UT WOS:000373073000007
PM 27003044
ER
PT J
AU Bandrowski, A
Brinkman, R
Brochhausen, M
Brush, MH
Bug, B
Chibucos, MC
Clancy, K
Courtot, M
Derom, D
Dumontier, M
Fan, LJ
Fostel, J
Fragoso, G
Gibson, F
Gonzalez-Beltran, A
Haendel, MA
He, YQ
Heiskanen, M
Hernandez-Boussard, T
Jensen, M
Lin, Y
Lister, AL
Lord, P
Malone, J
Manduchi, E
Mcgee, M
Morrison, N
Overton, JA
Parkinson, H
Peters, B
Rocca-Serra, P
Ruttenberg, A
Sansone, SA
Scheuermann, RH
Schober, D
Smith, B
Soldatova, LN
Stoeckert, CJ
Taylor, CF
Torniai, C
Turner, JA
Vita, R
Whetzel, PL
Zheng, J
AF Bandrowski, Anita
Brinkman, Ryan
Brochhausen, Mathias
Brush, Matthew H.
Bug, Bill
Chibucos, Marcus C.
Clancy, Kevin
Courtot, Melanie
Derom, Dirk
Dumontier, Michel
Fan, Liju
Fostel, Jennifer
Fragoso, Gilberto
Gibson, Frank
Gonzalez-Beltran, Alejandra
Haendel, Melissa A.
He, Yongqun
Heiskanen, Mervi
Hernandez-Boussard, Tina
Jensen, Mark
Lin, Yu
Lister, Allyson L.
Lord, Phillip
Malone, James
Manduchi, Elisabetta
McGee, Monnie
Morrison, Norman
Overton, James A.
Parkinson, Helen
Peters, Bjoern
Rocca-Serra, Philippe
Ruttenberg, Alan
Sansone, Susanna-Assunta
Scheuermann, Richard H.
Schober, Daniel
Smith, Barry
Soldatova, Larisa N.
Stoeckert, Christian J., Jr.
Taylor, Chris F.
Torniai, Carlo
Turner, Jessica A.
Vita, Randi
Whetzel, Patricia L.
Zheng, Jie
TI The Ontology for Biomedical Investigations
SO PLOS ONE
LA English
DT Article
ID FUNCTIONAL GENOMICS; MINIMUM INFORMATION; MICROARRAY DATA; OBO FOUNDRY;
STANDARDS; DATABASE; FORMAT; TAB; SPECIFICATION; FRAMEWORK
AB The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology. org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi. owl.
C1 [Bandrowski, Anita; Whetzel, Patricia L.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Brinkman, Ryan] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
[Brochhausen, Mathias] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Brush, Matthew H.; Haendel, Melissa A.; Torniai, Carlo] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Bug, Bill] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Chibucos, Marcus C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Clancy, Kevin] Thermo Fisher Sci, Carlsbad, CA USA.
[Courtot, Melanie] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Derom, Dirk] Vrije Univ Brussel, Brussels, Belgium.
[Dumontier, Michel; Hernandez-Boussard, Tina] Stanford Univ, Stanford, CA 94305 USA.
[Fan, Liju] Ontol Workshop LLC, Columbia, MD USA.
[Fostel, Jennifer] NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Fragoso, Gilberto] NIH, Ctr Biomed Informat & Informat Technol, Rockville, MD USA.
[Gibson, Frank] Royal Soc Chem, Cambridge, England.
[Gonzalez-Beltran, Alejandra; Lister, Allyson L.; Rocca-Serra, Philippe; Sansone, Susanna-Assunta] Univ Oxford, Oxford, England.
[He, Yongqun; Lin, Yu] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Heiskanen, Mervi] NCI, Rockville, MD USA.
[Jensen, Mark; Ruttenberg, Alan; Smith, Barry] Univ Buffalo, Buffalo, NY USA.
[Lord, Phillip] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Malone, James; Parkinson, Helen; Taylor, Chris F.] European Bioinformat Inst, European Mol Biol Lab, Hinxton, Cambs, England.
[Manduchi, Elisabetta; Stoeckert, Christian J., Jr.; Zheng, Jie] Univ Penn, Philadelphia, PA 19104 USA.
[McGee, Monnie] So Methodist Univ, Dallas, TX 75275 USA.
[Morrison, Norman] Univ Manchester, Manchester, England.
[Overton, James A.; Peters, Bjoern; Vita, Randi] La Jolla Inst Allergy & Immunol, La Jolla, CA USA.
[Scheuermann, Richard H.] J Craig Venter Inst, La Jolla, CA USA.
[Schober, Daniel] Leibniz Inst Plant Biochem, Halle, Saxony Anhalt, Germany.
[Soldatova, Larisa N.] Brunel Univ London, Uxbridge, Middx, England.
[Turner, Jessica A.] Georgia State Univ, Atlanta, GA 30303 USA.
RP Bandrowski, A (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA.
RI Brinkman, Ryan/B-1108-2008;
OI Brinkman, Ryan/0000-0002-9765-2990; Parkinson,
Helen/0000-0003-3035-4195; Gibson, Frank/0000-0003-3382-1748; Courtot,
Melanie/0000-0002-9551-6370; Bandrowski, Anita/0000-0002-5497-0243;
Chibucos, Marcus/0000-0001-9586-0780
FU National Institute of Allergy and Infectious Diseases [R01AI081062];
National Institutes of Health [R01GM093132, U01 DK 072473, P41 HG003619,
HHSN272201400030C, HHSN272201400028C, HHSN272201200010C, 1U19AI118626];
California Institute for Regenerative Medicine [GC1R-06673-B]; National
Science Foundation Division of Biological Infrastructure [1458400];
Engineering and Physical Sciences Research Council UK [EP/M015661/1,
EP/K030582/1]; European Network of Excellence (NoE) [503630];
Biotechnology and Biological Sciences Research Council [BB/E025080/1,
BB/G000638/1, BB/C008200/1, BB/I000917/1, BB/L024101/1]; European
Commission [H2020-EU.1.4.1.3 654241, H2020-EU.3.1634107]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (https://www.niaid.nih.gov/Pages/default.aspx)
R01AI081062 to YH, the National Institutes of Health
(http://www.nih.gov/) R01GM093132, U01 DK 072473, P41 HG003619 and
HHSN272201400030C to CJS, HHSN272201400028C to RHS, HHSN272201200010C
and 1U19AI118626 to BP, the California Institute for Regenerative
Medicine (https://www.cirm.ca.gov) GC1R-06673-B to RHS, the National
Science Foundation Division of Biological Infrastructure
(http://www.nsf.gov) 1458400 to MCC and the Engineering and Physical
Sciences Research Council UK (https://www.epsrc.ac.uk/) EP/M015661/1 and
EP/K030582/1 to LNS. This work was also supported by the European
Network of Excellence (NoE) (http://www.enfin.org) 503630 to DS, the
Biotechnology and Biological Sciences Research Council
(http://www.bbsrc.ac.uk) BB/E025080/1 and BB/G000638/1 to DS,
BB/C008200/1 to ALL, BB/I000917/1, BB/G000638/1, BB/E025080/1,
BB/L024101/1 to PRS, SAS, AGB and ALL and the European Commission
(https://ec.europa.eu/programmes/horizon2020) H2020-EU.1.4.1.3 654241
and H2020-EU.3.1634107 to PRS, SAS and AGB. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
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U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 29
PY 2016
VL 11
IS 4
AR e0154556
DI 10.1371/journal.pone.0154556
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK8XM
UT WOS:000375212600038
PM 27128319
ER
PT J
AU Yun, KJ
Han, K
Kim, MK
Park, YM
Baek, KH
Song, KH
Kwon, HS
AF Yun, Kyung-Jin
Han, Kyungdo
Kim, Mee Kyoung
Park, Yong-Moon
Baek, Ki-Hyun
Song, Ki-Ho
Kwon, Hyuk-Sang
TI Insulin Resistance Distribution and Cut-Off Value in Koreans from the
2008-2010 Korean National Health and Nutrition Examination Survey
SO PLOS ONE
LA English
DT Article
ID HOMEOSTASIS MODEL ASSESSMENT; METABOLIC SYNDROME;
CARDIOVASCULAR-DISEASE; POPULATION; GLUCOSE; INDEX; SENSITIVITY;
SECRETION; MENOPAUSE; NONOBESE
AB Background
We sought to identify the distribution and cut-off value of the 'homeostasis model assessment of insulin resistance' (HOMA-IR) according to gender and menopausal status for metabolic syndrome in Koreans.
Methods
Data were from the Korean National Health and Nutrition Examination Survey in 20082010. The subjects included adults aged 20 years or older. We excluded participants who had diabetes or fasting serum glucose >= 7 mmol/L. Finally, 11,121 subjects (4,911 men, 3,597 premenopausal women, 2,613 postmenopausal women) were enrolled. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome.
Results
The mean HOMA-IR was 2.11 (2.07-2.15) for men, 2.0 (1.97-2.04) for premenopausal women, and 2.14 (2.2-2.19) for postmenopausal women. The first cut-off values in men, premenopausal women, and postmenopausal women were 2.23 (sensitivity 70.6%, specificity 66.9%), 2.39 (sensitivity 72.3%, specificity 76.4%), and 2.48 (sensitivity 51.9%, specificity 80.2%), respectively. Based on the first HOMA-IR cut-off value, the prevalence of metabolic syndrome was 22.9% in men, 13.7% in premenopausal women, and 51.6% in postmenopausal women. The second cut-off value was around 3.2 in all three groups. Based on the second HOMA-IR cut-off value, the prevalence of metabolic syndrome was 50.8% in men, 42.5% in premenopausal women, and 71.6% in postmenopausal women.
Conclusion
In conclusion, the first cut-off values for HOMA-IR were 2.2-2.5 and the second cut-off value was 3.2 in Korea. The distribution of HOMA-IR showed differences according to gender and menopausal status. When we apply HOMA-IR, we should consider gender, menopausal status, and the prevalence of metabolic syndrome.
C1 [Yun, Kyung-Jin; Kim, Mee Kyoung; Baek, Ki-Hyun; Song, Ki-Ho; Kwon, Hyuk-Sang] Yeouido St Marys Hosp, Div Endocrinol & Metab, Dept Internal Med, Seoul, South Korea.
[Han, Kyungdo] Catholic Univ Korea, Dept Med Stat, Coll Med, Seoul, South Korea.
[Park, Yong-Moon] NIEHS, Dept Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kwon, HS (reprint author), Yeouido St Marys Hosp, Div Endocrinol & Metab, Dept Internal Med, Seoul, South Korea.
EM drkwon@catholic.ac.kr
OI PARK, YONG-MOON/0000-0002-5879-6879
NR 29
TC 2
Z9 2
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 29
PY 2016
VL 11
IS 4
AR e0154593
DI 10.1371/journal.pone.0154593
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK8XM
UT WOS:000375212600044
PM 27128847
ER
PT J
AU Terajima, M
Taga, Y
Chen, YL
Cabral, WA
Hou-Fu, G
Srisawasdi, S
Nagasawa, M
Sumida, N
Hattori, S
Kurie, JM
Marini, JC
Yamauchi, M
AF Terajima, Masahiko
Taga, Yuki
Chen, Yulong
Cabral, Wayne A.
Hou-Fu, Guo
Srisawasdi, Sirivimol
Nagasawa, Masako
Sumida, Noriko
Hattori, Shunji
Kurie, Jonathan M.
Marini, Joan C.
Yamauchi, Mitsuo
TI Cyclophilin-B Modulates Collagen Cross-linking by Differentially
Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains
of Tendon Type I Collagen
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LYSYL HYDROXYLASE; OSTEOGENESIS IMPERFECTA; BRUCK-SYNDROME; NULL MICE;
MUTATIONS; BONE; DEFICIENCY; PROTEIN; CELLS; EXPRESSION
AB Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet. 10, e1004465). However, the extent of decrease appears to be tissue-and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. Wefound that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1-3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation.
C1 [Terajima, Masahiko; Sumida, Noriko; Yamauchi, Mitsuo] Univ N Carolina, Sch Dent, North Carolina Oral Hlth Inst, Chapel Hill, NC 27599 USA.
[Taga, Yuki; Hattori, Shunji] Nippi Res Inst Biomatrix, Ibaraki 3020017, Japan.
[Chen, Yulong; Hou-Fu, Guo; Kurie, Jonathan M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.
[Cabral, Wayne A.; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
[Srisawasdi, Sirivimol] Chulalongkorn Univ, Dept Operat Dent, Bangkok 10330, Thailand.
[Nagasawa, Masako] Niigata Univ, Grad Sch Med & Dent Sci, Div Bioprosthodont, Niigata 9518514, Japan.
RP Yamauchi, M (reprint author), Univ N Carolina, Sch Dent, North Carolina Oral Hlth Inst, Chapel Hill, NC 27599 USA.
EM mitsuo_yamauchi@unc.edu
OI Taga, Yuki/0000-0001-9100-758X
FU National Institute of Health Grants, National Institutes of Health-NIAMS
[R21AR060978]; National Institute of Health Grants, National Institutes
of Health-NCI [R01CA105155]
FX This work was supported in part by National Institute of Health Grants,
National Institutes of Health-NIAMS R21AR060978, NCI R01CA105155. The
authors declare that they have no conflicts of interest with the
contents of this article. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 50
TC 4
Z9 4
U1 4
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 29
PY 2016
VL 291
IS 18
BP 9501
EP 9512
DI 10.1074/jbc.M115.699470
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL4JY
UT WOS:000375602300011
PM 26934917
ER
PT J
AU Knight, DK
Belenko, S
Wiley, T
Robertson, AA
Arrigona, N
Dennis, M
Bartkowski, JP
McReynolds, LS
Becan, JE
Knudsen, HK
Wasserman, GA
Rose, E
DiClemente, R
Leukefeld, C
AF Knight, Danica K.
Belenko, Steven
Wiley, Tisha
Robertson, Angela A.
Arrigona, Nancy
Dennis, Michael
Bartkowski, John P.
McReynolds, Larkin S.
Becan, Jennifer E.
Knudsen, Hannah K.
Wasserman, Gail A.
Rose, Eve
DiClemente, Ralph
Leukefeld, Carl
CA JJ-TRIALS Cooperative
TI Juvenile Justice-Translational Research on Interventions for Adolescents
in the Legal System (JJ-TRIALS): a cluster randomized trial targeting
system-wide improvement in substance use services
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Evidence-based practice implementation; System change; Interagency
collaboration; Substance use; Treatment services; Data-driven
decision-making; Juvenile justice; Adolescent; Justice-involved youth;
Cluster randomized trial
ID TIME-SERIES ANALYSIS; ABUSE TREATMENT; IMPLEMENTATION-RESEARCH;
INFORMATION-TECHNOLOGY; USE DISORDERS; DRUG COURT; HIV CARE; HEALTH;
ENGAGEMENT; PREVENTION
AB Background: The purpose of this paper is to describe the Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) study, a cooperative implementation science initiative involving the National Institute on Drug Abuse, six research centers, a coordinating center, and Juvenile Justice Partners representing seven US states. While the pooling of resources across centers enables a robust implementation study design involving 36 juvenile justice agencies and their behavioral health partner agencies, co-producing a study protocol that has potential to advance implementation science, meets the needs of all constituencies (funding agency, researchers, partners, study sites), and can be implemented with fidelity across the cooperative can be challenging. This paper describes (a) the study background and rationale, including the juvenile justice context and best practices for substance use disorders, (b) the selection and use of an implementation science framework to guide study design and inform selection of implementation components, and (c) the specific study design elements, including research questions, implementation interventions, measurement, and analytic plan.
Methods/design: The JJ-TRIALS primary study uses a head-to-head cluster randomized trial with a phased rollout to evaluate the differential effectiveness of two conditions (Core and Enhanced) in 36 sites located in seven states. A Core strategy for promoting change is compared to an Enhanced strategy that incorporates all core strategies plus active facilitation. Target outcomes include improvements in evidence-based screening, assessment, and linkage to substance use treatment.
Discussion: Contributions to implementation science are discussed as well as challenges associated with designing and deploying a complex, collaborative project.
C1 [Knight, Danica K.; Becan, Jennifer E.] Texas Christian Univ, Inst Behav Res, POB 32880, Ft Worth, TX 76129 USA.
[Belenko, Steven] Temple Univ, Dept Criminal Justice, Philadelphia, PA 19122 USA.
[Wiley, Tisha] NIDA, Bethseda, MD USA.
[Robertson, Angela A.] Mississippi State Univ, Social Sci Res Ctr, Starkville, MS USA.
[Arrigona, Nancy] Council State Govt Justice Ctr, Austin, TX USA.
[Dennis, Michael] Chestnut Hlth Syst, Normal, IL USA.
[Bartkowski, John P.] Univ Texas San Antonio, Dept Sociol, San Antonio, TX USA.
[McReynolds, Larkin S.; Wasserman, Gail A.] Columbia Univ NYSPI, Ctr Promot Mental Hlth Juvenile Justice, New York, NY USA.
[Knudsen, Hannah K.; Leukefeld, Carl] Univ Kentucky, Behav Sci, Lexington, KY USA.
[Rose, Eve; DiClemente, Ralph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Knight, DK (reprint author), Texas Christian Univ, Inst Behav Res, POB 32880, Ft Worth, TX 76129 USA.
EM d.knight@tcu.edu
FU JJ-TRIALS cooperative agreement, at the National Institute on Drug Abuse
(NIDA) by the National Institutes of Health (NIH); Chestnut Health
Systems [U01DA036221]; Columbia University [U01DA036226]; Emory
University [U01DA036233]; Mississippi State University [U01DA036176];
Temple University [U01DA036225]; Texas Christian University
[U01DA036224]; University of Kentucky [U01DA036158]
FX This study was funded under the JJ-TRIALS cooperative agreement, funded
at the National Institute on Drug Abuse (NIDA) by the National
Institutes of Health (NIH). The authors gratefully acknowledge the
collaborative contributions of NIDA and support from the following grant
awards: Chestnut Health Systems (U01DA036221); Columbia University
(U01DA036226); Emory University (U01DA036233); Mississippi State
University (U01DA036176); Temple University (U01DA036225); Texas
Christian University (U01DA036224); and University of Kentucky
(U01DA036158). NIDA Science Officer on this project is Tisha Wiley. The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official views of the NIDA,
NIH, or the participating universities or JJ systems.
NR 80
TC 2
Z9 2
U1 6
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD APR 29
PY 2016
VL 11
AR 57
DI 10.1186/s13012-016-0423-5
PG 18
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DK7MN
UT WOS:000375109900001
PM 27130175
ER
PT J
AU Park, JY
An, YR
An, CM
Kang, JH
Kim, EM
Kim, H
Cho, S
Kim, J
AF Park, Jung Youn
An, Yong-Rock
An, Chul-Min
Kang, Jung-Ha
Kim, Eun Mi
Kim, Heebal
Cho, Seoae
Kim, Jaemin
TI Evolutionary constraints over microsatellite abundance in larger mammals
as a potential mechanism against carcinogenic burden
SO SCIENTIFIC REPORTS
LA English
DT Article
ID METABOLIC-RATE; SIMPLE SEQUENCES; MOLECULAR CLOCK; BODY-SIZE; CANCER;
GENOME; TEMPERATURE; DNA; GENERATION; MUTATIONS
AB Larger organisms tend to live longer, have more potentially carcinogenic cells, and undergo more cell divisions. While one might intuitively expect cancer incidence to scale with body size, this assertion does not hold over the range of different mammals. Explaining this lack of correlation, so-called 'Peto's paradox' can likely increase our understanding of how cancer defense mechanisms are shaped by natural selection. Here, we study the occurrence of microsatellite in mammal genomes and observe that animals with expanded body size restrain the number of microsatellite. To take into account of higher mutation rate in the microsatellite region compared to that of genome, limiting the abundance of somatic mutations might explain how larger organisms could overcome the burden of cancer. These observations may serve as the basis to better understand how evolution has modeled protective mechanisms against cancer development.
C1 [Park, Jung Youn; An, Chul-Min; Kang, Jung-Ha; Kim, Eun Mi] Natl Fisheries Res & Dev Inst, Biotechnol Res Div, Busan 619705, South Korea.
[An, Yong-Rock] Natl Fisheries Res & Dev Inst, Cetacean Res Inst, Ulsan 680050, South Korea.
[Kim, Heebal] Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea.
[Kim, Heebal] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea.
[Kim, Heebal; Cho, Seoae] Seoul Natl Univ, C&K Genom, Res Pk, Seoul 151919, South Korea.
[Kim, Jaemin] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Cho, S (reprint author), Seoul Natl Univ, C&K Genom, Res Pk, Seoul 151919, South Korea.; Kim, J (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM seoae@cnkgenomics.com; jmkim85@snu.ac.kr
OI Kim, Heebal/0000-0003-3064-1303
FU National Fisheries Research and Development Institute (NFRDI)
[RP-2015-BT-009]; Marine Biotechnology Program (Genome Analysis of
Marine Organisms and Development of Functional Applications) - Ministry
of Oceans and Fisheries, Korea [PJT200620]
FX This work was funded by a grant from the National Fisheries Research and
Development Institute (NFRDI), contribution number RP-2015-BT-009. This
research was also supported by a grant from Marine Biotechnology Program
(PJT200620, Genome Analysis of Marine Organisms and Development of
Functional Applications) funded by Ministry of Oceans and Fisheries,
Korea.
NR 40
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 29
PY 2016
VL 6
AR 25246
DI 10.1038/srep25246
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK8NO
UT WOS:000375183800001
PM 27125812
ER
PT J
AU Van Boeckel, TP
Takahashi, S
Liao, QH
Xing, WJ
Lai, SJ
Hsiao, V
Liu, FF
Zheng, YM
Chang, ZR
Yuan, C
Metcalf, CJE
Yu, HJ
Grenfell, BT
AF Van Boeckel, Thomas P.
Takahashi, Saki
Liao, Qiaohong
Xing, Weijia
Lai, Shengjie
Hsiao, Victor
Liu, Fengfeng
Zheng, Yaming
Chang, Zhaorui
Yuan, Chen
Metcalf, C. Jessica E.
Yu, Hongjie
Grenfell, Bryan T.
TI Hand, Foot, and Mouth Disease in China: Critical Community Size and
Spatial Vaccination Strategies
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ENTEROVIRUS 71 VACCINE; MEASLES EPIDEMICS; DYNAMICS; OUTBREAK; MODEL;
TRANSMISSION; CHILDREN; SEASONALITY; INFECTIONS; SINGAPORE
AB Hand Foot and Mouth Disease (HFMD) constitutes a considerable burden for health care systems across China. Yet this burden displays important geographic heterogeneity that directly affects the local persistence and the dynamics of the disease, and thus the ability to control it through vaccination campaigns. Here, we use detailed geographic surveillance data and epidemic models to estimate the critical community size (CCS) of HFMD associated enterovirus serotypes CV-A16 and EV-A71 and we explore what spatial vaccination strategies may best reduce the burden of HFMD. We found CCS ranging from 336,979 (+/- 225,866) to 722,372 (+/- 150,562) with the lowest estimates associated with EV-A71 in the southern region of China where multiple transmission seasons have previously been identified. Our results suggest the existence of a regional immigration-recolonization dynamic driven by urban centers. If EV-A71 vaccines doses are limited, these would be optimally deployed in highly populated urban centers and in high-prevalence areas. If HFMD vaccines are included in China's National Immunization Program in order to achieve high coverage rates (> 85%), routine vaccination of newborns largely outperforms strategies in which the equivalent number of doses is equally divided between routine vaccination of newborns and pulse vaccination of the community at large.
C1 [Van Boeckel, Thomas P.; Takahashi, Saki; Hsiao, Victor; Metcalf, C. Jessica E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Van Boeckel, Thomas P.] ETH, Inst Integrat Biol, Zurich, Switzerland.
[Liao, Qiaohong; Xing, Weijia; Lai, Shengjie; Liu, Fengfeng; Zheng, Yaming; Chang, Zhaorui; Yuan, Chen; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Earlywarning Infect Dis, Beijing, Peoples R China.
[Xing, Weijia] Taishan Med Coll, Sch Publ Hlth, Jinan, Shandong, Peoples R China.
[Lai, Shengjie] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Metcalf, C. Jessica E.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Van Boeckel, TP (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.; Van Boeckel, TP (reprint author), ETH, Inst Integrat Biol, Zurich, Switzerland.; Yu, HJ (reprint author), Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Earlywarning Infect Dis, Beijing, Peoples R China.
EM thomas.vanboeckel@env.ethz.ch; yuhj@chinacdc.cn
FU National Science Fund for Distinguished Young Scholars [81525023];
National Natural Science Foundation of China [81473031]; Li Ka Shing
Oxford Global Health Programme [B9RST00-B900.57]; Science and Technology
Directorate, Department of Homeland Security contract
[HSHQDC-12-C-00058]; Bill and Melinda Gates Foundation; RAPIDD program
of the Science and Technology Directorate, Department of Homeland
Security; Fogarty International Center, national Institutes of Health;
ETH Zurich postdoctoral fellowship program; program for Adaptation to a
Changing Environment of ETH Zurich; Ministry of Science and Technology
of China [2012 ZX10004-201, 2014BAI13B05]; Flowminder Foundation,
Stockholm, Sweden
FX This work is funded by the National Science Fund for Distinguished Young
Scholars (No. 81525023) (Hongjie Yu), the National Natural Science
Foundation of China (No. 81473031) (Hongjie Yu), the Li Ka Shing Oxford
Global Health Programme (No. B9RST00-B900.57) (Hongjie Yu) the Science
and Technology Directorate, Department of Homeland Security contract
HSHQDC-12-C-00058 (B.T.G. and T.P.V.B.), the Bill and Melinda Gates
Foundation (B.T.G.), and the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, national Institutes of Health (B.T.G. and
C.J.E.M.). The ETH Zurich postdoctoral fellowship program (T.P.V.B), the
program for Adaptation to a Changing Environment of ETH Zurich
(T.P.V.B.), the National Natural Science Foundation of China (No.
81473031) (Hongjie Yu), the Ministry of Science and Technology of China
(2012 ZX10004-201 and 2014BAI13B05) (Hongjie Yu), National Science Fund
for Distinguished Young Scholars of China (No. 81525023) (Hongjie Yu)
and Flowminder Foundation, Stockholm, Sweden (Shengjie Lai). The funding
sources played no role in developing this paper and preparing it for
submission.
NR 47
TC 1
Z9 1
U1 12
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 29
PY 2016
VL 6
AR 25248
DI 10.1038/srep25248
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK8NR
UT WOS:000375184100001
PM 27125917
ER
PT J
AU Beck, DE
Reddy, PVN
Lv, W
Abdelmalak, M
Tender, GS
Lopez, S
Agama, K
Marchand, C
Pommier, Y
Cushman, M
AF Beck, Daniel E.
Reddy, P. V. Narasimha
Lv, Wei
Abdelmalak, Monica
Tender, Gabrielle S.
Lopez, Sophia
Agama, Keli
Marchand, Christophe
Pommier, Yves
Cushman, Mark
TI Investigation of the Structure-Activity Relationships of Aza-A-Ring
Indenoisoquinoline Topoisomerase I Poisons
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DNA PHOSPHODIESTERASE I; POTENTIAL ANTICANCER AGENTS; LACTAM SIDE-CHAIN;
BIOLOGICAL EVALUATION; CLEAVAGE COMPLEXES; MJ-III-65 NSC-706744;
INHIBITORS; CAMPTOTHECIN; MECHANISM; DRUG
AB Several indenoisoquinolines have shown promise as anticancer agents in clinical trials. Incorporation of a nitrogen atom modulating ligand-binding site interactions, physicochemical proper ties, and biological activities. Four series of aza-A-ring indenoisoquinolines were synthesized in which the nitrogen atom was systematically rotated through positions 1, 2, 3, and 4. The resulting compounds were tested to establish the optimal nitrogen position for topoisomerase IB (Topl) enzyme poisoning activity and cytotoxicity to human cancer cells. The 4-aza compounds were the most likely to yield derivatives with high Topl inhibitory activity. However, the relationship between structure and cytotoxicity was more complicated since the potency was influenced strongly by the side chains on the lactam nitrogen. The most cytotoxic azaindenoisoquinolines 45 and 46 had nitrogen in the 2- or 3 positions and a 3'-dimethylaminopropyl side chain, and they had MGM GI(50) values that were slightly better than the corresponding indenoisoquinoline 64.
C1 [Beck, Daniel E.; Reddy, P. V. Narasimha; Lv, Wei; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
[Beck, Daniel E.; Reddy, P. V. Narasimha; Lv, Wei; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
[Abdelmalak, Monica; Tender, Gabrielle S.; Lopez, Sophia; Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abdelmalak, Monica; Tender, Gabrielle S.; Lopez, Sophia; Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.; Cushman, M (reprint author), Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
EM cushman@purdue.edu
FU National Institutes of Health (NIH) [U01CA089566, P30CACA023168];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Developmental Therapeutics Program at the
National Cancer Institute [NO1-CO-56000]
FX This work was made possible by the National Institutes of Health (NIH)
through support with Research Grants U01CA089566 and P30CACA023168. This
research was also supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. In
vitro cytotoxicity testing was performed by the Developmental
Therapeutics Program at the National Cancer Institute, under contract
NO1-CO-56000.
NR 49
TC 3
Z9 3
U1 3
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD APR 28
PY 2016
VL 59
IS 8
BP 3840
EP 3853
DI 10.1021/acs.jmedchem.6b00003
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DL3FP
UT WOS:000375519900017
PM 27070999
ER
PT J
AU Shah, R
Tanriverdi, K
Levy, D
Larson, M
Gerstein, M
Mick, E
Rozowsky, J
Kitchen, R
Murthy, V
Mikalev, E
Freedman, JE
AF Shah, Ravi
Tanriverdi, Kahraman
Levy, Daniel
Larson, Martin
Gerstein, Mark
Mick, Eric
Rozowsky, Joel
Kitchen, Robert
Murthy, Venkatesh
Mikalev, Ekaterina
Freedman, Jane E.
TI Discordant Expression of Circulating microRNA from Cellular and
Extracellular Sources
SO PLOS ONE
LA English
DT Article
ID PLATELET; TRANSCRIPTOME; BLOOD
AB MicroRNA (miRNA) expression has rapidly grown into one of the largest fields for disease characterization and development of clinical biomarkers. Consensus is lacking in regards to the optimal sample source or if different circulating sources are concordant. Here, using miRNA measurements from contemporaneously obtained whole blood-and plasma-derived RNA from 2391 individuals, we demonstrate that plasma and blood miRNA levels are divergent and may reflect different biological processes and disease associations.
C1 [Shah, Ravi] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Tanriverdi, Kahraman; Mikalev, Ekaterina; Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA.
[Levy, Daniel; Larson, Martin] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Levy, Daniel; Larson, Martin] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gerstein, Mark; Rozowsky, Joel; Kitchen, Robert] Yale Univ, Sch Med, Computat Biol & Bioinformat Program, 333 Cedar St, New Haven, CT 06520 USA.
[Mick, Eric] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA.
[Murthy, Venkatesh] Univ Michigan, Dept Cardiol, 1500 E Med Ctr Dr SPC 5873, Ann Arbor, MI 48109 USA.
RP Freedman, JE (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA.
EM jane.freedman@umassmed.edu
OI Murthy, Venkatesh/0000-0002-7901-1321; Rozowsky,
Joel/0000-0002-3565-0762
FU National Institutes of Health (NIH) as part of the NIH Common Fund,
through the Office of Strategic Coordination/Office of the NIH Director
[N01-HC 25195, P01-HL085381, UH2TR000921, U01HL126495]
FX This work was supported by National Institutes of Health (NIH) grants
N01-HC 25195, P01-HL085381 (to J.E.F.); UH2TR000921 and U01HL126495 (to
J.E.F.; www.nih.gov), as part of the NIH Common Fund, through the Office
of Strategic Coordination/Office of the NIH Director.
NR 19
TC 4
Z9 4
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 28
PY 2016
VL 11
IS 4
AR e0153691
DI 10.1371/journal.pone.0153691
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK8XE
UT WOS:000375211700023
PM 27123852
ER
PT J
AU Ewer, K
Rampling, T
Venkatraman, N
Bowyer, G
Wright, D
Lambe, T
Imoukhuede, EB
Payne, R
Fehling, SK
Strecker, T
Biedenkopf, N
Krahling, V
Tully, CM
Edwards, NJ
Bentley, EM
Samuel, D
Labbe, G
Jin, J
Gibani, M
Minhinnick, A
Wilkie, M
Poulton, I
Lella, N
Roberts, R
Hartnell, F
Bliss, C
Sierra-Davidson, K
Powlson, J
Berrie, E
Tedder, R
Roman, F
De Ryck, I
Nicosia, A
Sullivan, NJ
Stanley, DA
Mbaya, OT
Ledgerwood, JE
Schwartz, RM
Siani, L
Colloca, S
Folgori, A
Di Marco, S
Cortese, R
Wright, E
Becker, S
Graham, BS
Koup, RA
Levine, MM
Volkmann, A
Chaplin, P
Pollard, AJ
Draper, SJ
Ballou, WR
Lawrie, A
Gilbert, SC
Hill, AVS
AF Ewer, K.
Rampling, T.
Venkatraman, N.
Bowyer, G.
Wright, D.
Lambe, T.
Imoukhuede, E. B.
Payne, R.
Fehling, S. K.
Strecker, T.
Biedenkopf, N.
Kraehling, V.
Tully, C. M.
Edwards, N. J.
Bentley, E. M.
Samuel, D.
Labbe, G.
Jin, J.
Gibani, M.
Minhinnick, A.
Wilkie, M.
Poulton, I.
Lella, N.
Roberts, R.
Hartnell, F.
Bliss, C.
Sierra-Davidson, K.
Powlson, J.
Berrie, E.
Tedder, R.
Roman, F.
De Ryck, I.
Nicosia, A.
Sullivan, N. J.
Stanley, D. A.
Mbaya, O. T.
Ledgerwood, J. E.
Schwartz, R. M.
Siani, L.
Colloca, S.
Folgori, A.
Di Marco, S.
Cortese, R.
Wright, E.
Becker, S.
Graham, B. S.
Koup, R. A.
Levine, M. M.
Volkmann, A.
Chaplin, P.
Pollard, A. J.
Draper, S. J.
Ballou, W. R.
Lawrie, A.
Gilbert, S. C.
Hill, A. V. S.
TI A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PROTECTS NONHUMAN-PRIMATES; IMMUNITY; VIRUS; CHALLENGE; INFECTION;
HUMANS
AB BACKGROUND
The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak.
METHODS
In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels - 1x10(10) viral particles, 2.5x10(10) viral particles, and 5x10(10) viral particles - with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability.
RESULTS
No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001).
CONCLUSIONS
The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone.
C1 [Ewer, K.; Rampling, T.; Venkatraman, N.; Bowyer, G.; Wright, D.; Lambe, T.; Imoukhuede, E. B.; Payne, R.; Tully, C. M.; Edwards, N. J.; Labbe, G.; Jin, J.; Gibani, M.; Minhinnick, A.; Wilkie, M.; Poulton, I.; Lella, N.; Roberts, R.; Hartnell, F.; Bliss, C.; Sierra-Davidson, K.; Powlson, J.; Berrie, E.; Pollard, A. J.; Draper, S. J.; Lawrie, A.; Gilbert, S. C.; Hill, A. V. S.] Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
[Ewer, K.; Rampling, T.; Venkatraman, N.; Bowyer, G.; Wright, D.; Lambe, T.; Imoukhuede, E. B.; Payne, R.; Tully, C. M.; Edwards, N. J.; Labbe, G.; Jin, J.; Gibani, M.; Minhinnick, A.; Wilkie, M.; Poulton, I.; Lella, N.; Roberts, R.; Hartnell, F.; Bliss, C.; Sierra-Davidson, K.; Powlson, J.; Berrie, E.; Pollard, A. J.; Draper, S. J.; Lawrie, A.; Gilbert, S. C.; Hill, A. V. S.] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford OX3 7DQ, England.
[Ewer, K.; Rampling, T.; Venkatraman, N.; Bowyer, G.; Wright, D.; Lambe, T.; Imoukhuede, E. B.; Payne, R.; Tully, C. M.; Edwards, N. J.; Labbe, G.; Jin, J.; Gibani, M.; Minhinnick, A.; Wilkie, M.; Poulton, I.; Lella, N.; Roberts, R.; Hartnell, F.; Bliss, C.; Sierra-Davidson, K.; Powlson, J.; Berrie, E.; Pollard, A. J.; Draper, S. J.; Lawrie, A.; Gilbert, S. C.; Hill, A. V. S.] Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England.
[Bentley, E. M.; Wright, E.] Univ Westminster, Fac Sci & Technol, Viral Pseudotype Unit, London W1R 8AL, England.
[Samuel, D.; Tedder, R.] Publ Hlth Agcy, Virus Reference Dept, London, England.
[Fehling, S. K.; Strecker, T.; Biedenkopf, N.; Kraehling, V.; Becker, S.] Univ Marburg, Inst Virol, D-35032 Marburg, Germany.
[Becker, S.] German Ctr Infect Res, Partner Site Giessen Marburg Langen, Marburg, Germany.
[Volkmann, A.; Chaplin, P.] Bavarian Nord, Martinsried, Germany.
[Roman, F.; De Ryck, I.; Ballou, W. R.] GlaxoSmithKline Biol, Rixensart, Belgium.
[Nicosia, A.; Siani, L.; Colloca, S.; Folgori, A.; Di Marco, S.] ReiThera, Rome, Italy.
[Nicosia, A.] Univ Naples Federico II, CEINGE, Naples, Italy.
[Nicosia, A.] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy.
[Sullivan, N. J.; Stanley, D. A.; Mbaya, O. T.; Ledgerwood, J. E.; Schwartz, R. M.; Graham, B. S.; Koup, R. A.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Levine, M. M.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Cortese, R.] Keires, Basel, Switzerland.
RP Hill, AVS (reprint author), Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
EM adrian.hill@ndm.ox.ac.uk
OI Wright, Edward/0000-0001-7041-5138; Bentley, Emma M./0000-0001-6109-2840
FU Wellcome Trust
FX Funded by the Wellcome Trust and others; ClinicalTrials.gov number,
NCT02240875.
NR 30
TC 24
Z9 24
U1 4
U2 8
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 28
PY 2016
VL 374
IS 17
BP 1635
EP 1646
DI 10.1056/NEJMoa1411627
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DK3UR
UT WOS:000374843400007
PM 25629663
ER
PT J
AU Porter, JR
Fisher, BE
Batchelor, E
AF Porter, Joshua R.
Fisher, Brian E.
Batchelor, Eric
TI p53 Pulses Diversify Target Gene Expression Dynamics in an mRNA
Half-Life-Dependent Manner and Delineate Co-regulated Target Gene
Subnetworks
SO CELL SYSTEMS
LA English
DT Article
ID P53-MDM2 FEEDBACK LOOP; DNA-DAMAGE; CELLS; NOISE; TRANSCRIPTION;
TRANSMISSION; OSCILLATIONS; ACTIVATION; INDUCTION; NETWORKS
AB The transcription factor p53 responds to DNA double-strand breaks by increasing in concentration in a series of pulses of fixed amplitude, duration, and period. How p53 pulses influence the dynamics of p53 target gene expression is not understood. Here, we show that, in bulk cell populations, patterns of p53 target gene expression cluster into groups with stereotyped temporal behaviors, including pulsing and rising dynamics. These behaviors correlate statistically with the mRNA decay rates of target genes: short mRNA half-lives produce pulses of gene expression. This relationship can be recapitulated by mathematical models of p53-dependent gene expression in single cells and cell populations. Single-cell transcriptional profiling demonstrates that expression of a subset of p53 target genes is coordinated across time within single cells; p53 pulsing attenuates this coordination. These results help delineate how p53 orchestrates the complex DNA damage response and give insight into the function of pulsatile signaling pathways.
C1 [Porter, Joshua R.; Fisher, Brian E.; Batchelor, Eric] NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
RP Batchelor, E (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
EM batchelore@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute, CCR
FX We thank W. Telford and V. Kapoor in the Center for Cancer Research
(CCR) ETIB Flow Cytometry Core for aid in single-cell sorting as well as
M. Raffeld and the CCR Molecular Diagnostics Unit and J. Zhu and the
National Heart, Lung, and Blood Institute DNA Sequencing and Genomics
Core for help with single cell transcriptional profiling. We also thank
D. Levens, the Levens lab, A. Moody, A. Sun, T. Przytycka, C. Parent, J.
Oberholtzer, A. Loewer, L. Goentoro, J. Hansen, J. Stommel, and J. Luo
for helpful discussions. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, CCR.
NR 32
TC 1
Z9 1
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2405-4712
EI 2405-4720
J9 CELL SYST
JI Cell Syst.
PD APR 27
PY 2016
VL 2
IS 4
BP 272
EP 282
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA EL1CY
UT WOS:000394359300010
PM 27135539
ER
PT J
AU Kohn, EC
Ivy, SP
AF Kohn, Elise C.
Ivy, S. Percy
TI Confronting the Care Delivery Challenges Arising from Precision Medicine
SO FRONTIERS IN ONCOLOGY
LA English
DT Article
DE precision medicine; biomarkers; targets; genetic testing; opportunities;
obstacles
ID CELL LUNG-CANCER; ENDOMETRIAL CANCER; OVARIAN-CANCER; METHOD VALIDATION;
DRUG DEVELOPMENT; CLINICAL-TRIALS; BIOMARKERS; MANAGEMENT; CARCINOMA;
TUMOR
AB Understanding the biology of cancer at the cellular and molecular levels, and the application of such knowledge to the patient, has opened new opportunities and uncovered new obstacles to quality cancer care delivery. Benefits include our ability to now understand that many, if not most, cancers are not one-size-fits-all. Cancers are a variety of diseases for which intervention may be very different. This approach is beginning to bear fruit in gynecologic cancers where we are investigating therapeutic optimization at a more focused level, that while not yet precision care, is perhaps much improved. Obstacles to quality care for patients come from many directions. These include incomplete understanding of the role of the mutant proteins in the cancers, the narrow spectrum of agents, broader mutational profiles in solid tumors, and sometimes overzealous application of the findings of genetic testing. This has been further compromised by the unbridled use of social media by all stakeholders in cancer care often without scientific qualification, where anecdote sometimes masquerades as a fact. The only current remedy is to wave the flag of caution, encourage all patients who undergo genetic testing, either germline or somatic, to do so with the oversight of genetic counselors and physician scientists knowledgeable in the pathways involved. This aspiration is accomplished with well-designed clinical trials that inform next steps in this complex and ever evolving process.
C1 [Kohn, Elise C.; Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Div Canc Therapy & Diag, Rockville, MD USA.
RP Kohn, EC (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Therapy & Diag, Rockville, MD USA.
EM kohne@mail.nih.gov
NR 40
TC 1
Z9 1
U1 1
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD APR 27
PY 2016
VL 6
AR 106
DI 10.3389/fonc.2016.00106
PG 7
WC Oncology
SC Oncology
GA DK3OZ
UT WOS:000374828200001
PM 27200294
ER
PT J
AU Roseland, JM
Patterson, KY
Andrews, KW
Phillips, KM
Phillips, MM
Pehrsson, PR
Dufresne, GL
Jakobsen, J
Gusev, PA
Savarala, S
Nguyen, QV
Makowski, AJ
Scheuerell, CR
Larouche, GP
Wise, SA
Harnly, JM
Williams, JR
Betz, JM
Taylor, CL
AF Roseland, Janet Maxwell
Patterson, Kristine Y.
Andrews, Karen W.
Phillips, Katherine M.
Phillips, Melissa M.
Pehrsson, Pamela R.
Dufresne, Guy L.
Jakobsen, Jette
Gusev, Pavel A.
Savarala, Sushma
Nguyen, Quynhanh V.
Makowski, Andrew J.
Scheuerell, Chad R.
Larouche, Guillaume P.
Wise, Stephen A.
Harnly, James M.
Williams, Juhi R.
Betz, Joseph M.
Taylor, Christine L.
TI Interlaboratory Trial for Measurement of Vitamin D and 25-Hydroxyvitamin
D [25(OH)D] in Foods and a Dietary Supplement Using Liquid
Chromatography-Mass Spectrometry
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE reference material; food; dietary supplement; vitamin D-3
(cholecalciferol); 25-hydroxyvitamin D-3 (25-hydroxycholcalciferol)
ID NUTRIENT ANALYSIS PROGRAM; CARDIOVASCULAR-DISEASE; BIOLOGICAL-ACTIVITY;
NATIONAL FOOD; D-3; SERUM; EGGS; MEAT; HEALTH; FISH
AB Assessment of total vitamin D intake from foods and dietary supplements (DSs) may be incomplete if 25-hydroxyvitamin D [25(OH)D] intake is not included. However, 25(OH)D data for such intake assessments are lacking, no food or DS reference materials (RMs) are available, and comparison of laboratory performance has been needed. The primary goal of this study was to evaluate whether vitamin D-3 and 25(OH)D-3 concentrations in food and DS materials could be measured with acceptable reproducibility. Five experienced laboratories from the United States and other countries participated, all using liquid chromatography tandem mass spectrometry but no common analytical protocol; however, various methods were used for determining vitamin D-3 in the DS. Five animal-based materials (including three commercially available RMs) and one DS were analyzed. Reproducibility results for the materials were acceptable. Thus, it is possible to obtain consistent results among experienced laboratories for vitamin D-3 and 25(OH)D-3, in foods and a DS.
C1 [Roseland, Janet Maxwell; Patterson, Kristine Y.; Andrews, Karen W.; Pehrsson, Pamela R.; Gusev, Pavel A.; Savarala, Sushma; Nguyen, Quynhanh V.; Williams, Juhi R.] USDA ARS, Nutrient Data Lab, BARC West, 10300 Baltimore Ave,Bldg 005, Beltsville, MD 20705 USA.
[Phillips, Katherine M.] Virginia Tech, Biochem Dept 0308, 304 Engel Hall, Blacksburg, VA 24061 USA.
[Phillips, Melissa M.; Wise, Stephen A.] NIST, Div Chem Sci, MS 8392,100 Bur Dr, Gaithersburg, MD 20899 USA.
[Dufresne, Guy L.] Hlth Canada, Food & Nutr Lab, 1001 St Laurent Ouest, Longueuil, PQ J4K 1C7, Canada.
[Jakobsen, Jette] Tech Univ Denmark, Natl Food Inst, Div Food Chem, Soborg, Denmark.
[Makowski, Andrew J.] Heartland Assays LLC, Suite 4400,2711 South Loop Dr, Ames, IA 50010 USA.
[Scheuerell, Chad R.] Covance Labs, 3301 Kinsman Blvd, Madison, WI 53704 USA.
[Betz, Joseph M.; Taylor, Christine L.] NIH, Off Dietary Supplements, 3B01,MSC 7517,6100 Execut Blvd, Bethesda, MD 20892 USA.
[Harnly, James M.] USDA ARS, Food Composit & Method Dev Lab, BARC East, Bldg 161,10300 Baltimore Ave, Beltsville, MD 20705 USA.
RP Roseland, JM (reprint author), USDA ARS, Nutrient Data Lab, BARC West, 10300 Baltimore Ave,Bldg 005, Beltsville, MD 20705 USA.
EM janet.roseland@ars.usda.gov
FU Office of Dietary Supplements of the National Institutes of Health [60
1235 3012]
FX Partial funding for this work was provided under Agreement 60 1235 3012
from Office of Dietary Supplements of the National Institutes of Health.
NR 47
TC 0
Z9 0
U1 5
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD APR 27
PY 2016
VL 64
IS 16
BP 3167
EP 3175
DI 10.1021/acs.jafc.5b05016
PG 9
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA DK9IO
UT WOS:000375244300008
PM 27045951
ER
PT J
AU Thrane, S
Janitzek, CM
Matondo, S
Resende, M
Gustavsson, T
de Jongh, WA
Clemmensen, S
Roeffen, W
van de Vegte-Bolmer, M
van Gemert, GJ
Sauerwein, R
Schiller, JT
Nielsen, MA
Theander, TG
Salanti, A
Sander, AF
AF Thrane, Susan
Janitzek, Christoph M.
Matondo, Sungwa
Resende, Mafalda
Gustavsson, Tobias
de Jongh, Willem Adriaan
Clemmensen, Stine
Roeffen, Will
van de Vegte-Bolmer, Marga
van Gemert, Geert Jan
Sauerwein, Robert
Schiller, John T.
Nielsen, Morten A.
Theander, Thor G.
Salanti, Ali
Sander, Adam F.
TI Bacterial superglue enables easy development of efficient virus-like
particle based vaccines
SO JOURNAL OF NANOBIOTECHNOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM PARASITES; TRANSMISSION-BLOCKING ACTIVITY;
PREGNANCY-ASSOCIATED MALARIA; ANTIBODY-RESPONSES; IMMUNODEFICIENCY
VIRUS; IMMUNE-RESPONSE; CORE PARTICLES; PROTEIN; ANTIGEN; PFS25
AB Background: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP components.
Results: Genetic fusion of SpyTag or SpyCatcher to the N-terminus and/or C-terminus of the Acinetobacter phage AP205 capsid protein resulted in formation of stable, nonaggregated VLPs expressing one SpyCatcher, one SpyTag or two SpyTags per capsid protein. Mixing of spy-VLPs with eleven different vaccine antigens fused to SpyCatcher or SpyTag resulted in formation of antigen-VLP complexes with coupling efficiencies (% occupancy of total VLP binding sites) ranging from 22-88 %. In mice, spy-VLP vaccines presenting the malaria proteins Pfs25 or VAR2CSA markedly increased antibody titer, affinity, longevity and functional efficacy compared to corresponding vaccines employing monomeric proteins. The spy-VLP vaccines also effectively broke B cell self-tolerance and induced potent and durable antibody responses upon vaccination with cancer or allergy-associated self-antigens (PD-L1, CTLA-4 and IL-5).
Conclusions: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well as to efficiently break B cell self-tolerance. The spy-VLP-system may serve as a generic tool for the cost-effective development of effective VLP-vaccines against both infectious-and non-communicable diseases and could facilitate rapid and unbiased screening of vaccine candidate antigens.
C1 [Thrane, Susan; Janitzek, Christoph M.; Resende, Mafalda; Gustavsson, Tobias; Clemmensen, Stine; Nielsen, Morten A.; Theander, Thor G.; Salanti, Ali; Sander, Adam F.] Univ Copenhagen, Dept Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark.
[Thrane, Susan; Janitzek, Christoph M.; Resende, Mafalda; Gustavsson, Tobias; Clemmensen, Stine; Nielsen, Morten A.; Theander, Thor G.; Salanti, Ali; Sander, Adam F.] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen, Denmark.
[Matondo, Sungwa] KCMC, Kilimanjaro Clin Res Inst, Moshi, Tanzania.
[de Jongh, Willem Adriaan; Clemmensen, Stine] ExpreS2 Biotechnol, SCION DTU Sci Pk, Horsholm, Denmark.
[Roeffen, Will; van de Vegte-Bolmer, Marga; van Gemert, Geert Jan; Sauerwein, Robert] Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Salanti, A; Sander, AF (reprint author), Univ Copenhagen, Dept Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark.
EM salanti@sund.ku.dk; adamsander@gmail.com
OI Theander, Thor G./0000-0002-3509-7514
FU PATH Malaria Vaccine Initiative; Danish Research Council [13127];
European Union [304815]; Bill and Melinda Gates Foundation [APP178218]
FX The authors would like to thank Jens Hedelund Madsen, Anne Corfitz,
Elham Marjan Mohammad Alijazaeri and Nahla Chehabi for technical
assistance. We would like to thank Susheel Kumar Sinhg for the kind
donation of mAb 4B7 and The Biophysics Facility-Protein Structure and
Function Program from Center for Protein Research, Copenhagen, for
assisting us with DLS measurements. We would like to thank Dr. Carole
Long and Dr. Kazutoyo Miura, NIH, for assisting with SMFA analysis, and
the PATH Malaria Vaccine Initiative for their funding support to the NIH
for this effort. This study was supported by DANIDA, IdMalVac from the
Danish Research Councils (Grant 13127), PlacMalVac under the European
Union Seventh Framework Programme, FP7-HEALTH-2012-INNOVATION under
grant agreement no. 304815 and through a grant from Bill and Melinda
Gates Foundation Grant ID APP178218.
NR 61
TC 6
Z9 6
U1 9
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-3155
J9 J NANOBIOTECHNOL
JI J. Nanobiotechnol.
PD APR 27
PY 2016
VL 14
AR 30
DI 10.1186/s12951-016-0181-1
PG 16
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA DK5EP
UT WOS:000374942800001
PM 27117585
ER
PT J
AU Jasmin, KM
McGettigan, C
Agnew, ZK
Lavan, N
Josephs, O
Cummins, F
Scott, SK
AF Jasmin, Kyle M.
McGettigan, Carolyn
Agnew, Zarinah K.
Lavan, Nadine
Josephs, Oliver
Cummins, Fred
Scott, Sophie K.
TI Cohesion and Joint Speech: Right Hemisphere Contributions to
Synchronized Vocal Production
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE coordinated action; fMRI; joint speech; right hemisphere; social
cohesion; speech control
ID SENSORIMOTOR SYNCHRONIZATION; AUDITORY-CORTEX; NONHUMAN-PRIMATES;
FEEDBACK-CONTROL; NEURAL BASIS; SELF-FACE; CONVERSATION; COORDINATION;
BRAIN; COMMUNICATION
AB Synchronized behavior (chanting, singing, praying, dancing) is found in all human cultures and is central to religious, military, and political activities, which require people to act collaboratively and cohesively; however, we know little about the neural underpinnings of many kinds of synchronous behavior (e.g., vocal behavior) or its role in establishing and maintaining group cohesion. In the present study, we measured neural activity using fMRI while participants spoke simultaneously with another person. We manipulated whether the couple spoke the same sentence (allowing synchrony) or different sentences (preventing synchrony), and also whether the voice the participant heard was "live" (allowing rich reciprocal interaction) or prerecorded (with no such mutual influence). Synchronous speech was associated with increased activity in posterior and anterior auditory fields. When, and only when, participants spoke with a partner who was both synchronous and "live," we observed a lack of the suppression of auditory cortex, which is commonly seen as a neural correlate of speech production. Instead, auditory cortex responded as though it were processing another talker's speech. Our results suggest that detecting synchrony leads to a change in the perceptual consequences of one'sownactions: they are processed as though they were other-, rather than self-produced. This may contribute to our understanding of synchronized behavior as a group-bonding tool.
C1 [Jasmin, Kyle M.; McGettigan, Carolyn; Scott, Sophie K.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England.
[Jasmin, Kyle M.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20492 USA.
[McGettigan, Carolyn; Lavan, Nadine] Univ London, Dept Psychol, London TW20 0EX, England.
[Agnew, Zarinah K.] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA.
[Josephs, Oliver] UCL, Inst Neurol, London WC1N 3BG, England.
[Cummins, Fred] Univ Coll Dublin, Sch Comp Sci, Dublin 4, Ireland.
RP Scott, SK (reprint author), 17 Queen Sq, London WC1N 3AR, England.
EM sophie.scott@ucl.ac.uk
RI Scott, Sophie/A-1843-2010; McGettigan, Carolyn/A-3660-2010
OI Scott, Sophie/0000-0001-7510-6297; McGettigan,
Carolyn/0000-0001-6293-3795
FU University College London National Institute of Mental Health; Wellcome
Trust [WT090961MA]
FX This work was supported by a University College London National
Institute of Mental Health Joint Doctoral Training Program in
Neuroscience Award to K.M.J., and a Wellcome Trust Senior Research
Fellowship in Biomedical (no. WT090961MA) Science to S.K.S.
NR 63
TC 1
Z9 1
U1 4
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 27
PY 2016
VL 36
IS 17
BP 4669
EP 4680
DI 10.1523/JNEUROSCI.4075-15.2016
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DK7UF
UT WOS:000375130500003
PM 27122026
ER
PT J
AU Papaleo, F
Yang, F
Paterson, C
Palumbo, S
Carr, GV
Wang, YH
Floyd, K
Huang, WW
Thomas, CJ
Chen, JS
Weinberger, DR
Law, AJ
AF Papaleo, Francesco
Yang, Feng
Paterson, Clare
Palumbo, Sara
Carr, Gregory V.
Wang, Yanhong
Floyd, Kirsten
Huang, Wenwei
Thomas, Craig J.
Chen, Jingshan
Weinberger, Daniel R.
Law, Amanda J.
TI Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic
Neuregulin1 (NRG1-IV) Murine Schizophrenia Model
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE AKT; ErbB; IC87114; neuregulin; PIK3CD; schizophrenia
ID LONG-TERM POTENTIATION; PARVALBUMIN-POSITIVE INTERNEURONS; CORTICAL
PYRAMIDAL NEURONS; WORKING-MEMORY; COGNITIVE IMPAIRMENT; RECOGNITION
MEMORY; PREFRONTAL CORTEX; SOCIAL COGNITION; BIPOLAR DISORDER; CANDIDATE
GENES
AB Schizophrenia is a chronic, disabling neuropsychiatric disorder with complex genetic origins. The development of strategies for genome manipulation in rodents provides a platform for understanding the pathogenic role of genes and for testing novel therapeutic agents. Neuregulin 1 (NRG1), a critical developmental neurotrophin, is associated with schizophrenia. The NRG1 gene undergoes extensive alternative splicing and, to date, little is known about the neurobiology of a novel NRG1 isoform, NRG1-IV, which is increased in the brains of individuals with schizophrenia and associated with genetic risk variation. Here, we developed a transgenic mouse model (NRG1-IV/NSE-tTA) in which human NRG1-IV is selectively overexpressed in a neuronal specific manner. Using a combination of molecular, biochemical, electrophysiological, and behavioral analyses, we demonstrate that NRG1-IV/NSE-tTA mice exhibit abnormal behaviors relevant to schizophrenia, including impaired sensorimotor gating, discrimination memory, and social behaviors. These neurobehavioral phenotypes are accompanied by increases in cortical expression of the NRG1 receptor, ErbB4 and the downstream signaling target, PIK3-p110 delta, along with disrupted dendritic development, synaptic pathology, and altered prefrontal cortical excitatory-inhibitory balance. Pharmacological inhibition of p110 delta reversed sensorimotor gating and cognitive deficits. These data demonstrate a novel role for NRG1-IV in learning, memory, and neural circuit formation and a potential neurobiological mechanism for schizophrenia risk; show that deficits are pharmacologically reversible in adulthood; and further highlight p110 delta as a target for antipsychotic drug development.
C1 [Papaleo, Francesco; Yang, Feng; Palumbo, Sara; Carr, Gregory V.; Wang, Yanhong; Chen, Jingshan; Weinberger, Daniel R.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy.
[Yang, Feng; Wang, Yanhong; Weinberger, Daniel R.] Lieber Inst Brain Dev, Johns Hopkins Univ Med Campus, Baltimore, MD 21205 USA.
[Paterson, Clare; Floyd, Kirsten; Law, Amanda J.] Univ Colorado, Sch Med, Dept Psychiat, 12700 East 19th Ave,Mailstop 8619,RC2,Rm 4100C, Aurora, CO 80045 USA.
[Palumbo, Sara; Carr, Gregory V.] Univ Pisa, Dept Surg Med & Mol Pathol, Lab Mol Biol, I-56126 Pisa, Italy.
[Palumbo, Sara; Carr, Gregory V.] Univ Pisa, Crit Care, I-56126 Pisa, Italy.
[Huang, Wenwei; Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Law, Amanda J.] Univ Colorado, Sch Med, Dept Cell & Dev Biol, 12700 East 19th Ave,Mailstop 8619,RC2,Rm 4100C, Aurora, CO 80045 USA.
RP Law, AJ (reprint author), Univ Colorado, Sch Med, Dept Psychiat, 12700 East 19th Ave,Mailstop 8619,RC2,Rm 4100C, Aurora, CO 80045 USA.; Law, AJ (reprint author), Univ Colorado, Sch Med, Dept Cell & Dev Biol, 12700 East 19th Ave,Mailstop 8619,RC2,Rm 4100C, Aurora, CO 80045 USA.
EM amanda.law@ucdenver.edu
RI palumbo, sara/B-1603-2013; Carr, Gregory/M-8821-2016;
OI palumbo, sara/0000-0002-3809-6058; Carr, Gregory/0000-0002-6091-6729;
Papaleo, Francesco/0000-0002-6326-0657; Law, Amanda/0000-0002-2574-1564
FU National Institute of Mental Health (NIMH) Intramural Research Program,
National Institutes of Health (NIH); NIH, NIMH [P50 MH-086383-06, R01
MH103716-02]; Brain and Behavior Research Foundation/NARSAD; Dr. Nancy
Gary Endowed Chair in Children's Mental Health Disorders
FX This work was supported by funding from the National Institute of Mental
Health (NIMH) Intramural Research Program, National Institutes of Health
(NIH) to A.J.L and D.R.W., and by extramural funding from the NIH, NIMH
to A.J.L (P50 MH-086383-06 and R01 MH103716-02). Support was also
provided by the Sidney R. Baer, Jr. Award. Outstanding Research
Achievement Prize for Schizophrenia Research from the Brain and Behavior
Research Foundation/NARSAD and the Dr. Nancy Gary Endowed Chair in
Children's Mental Health Disorders, both held by A.J.L. We thank Dr.
James Pickel and the NIMH Division of Intramural Programs, Transgenic
Core Facility for mouse oocyte injections, Mr. Qingjun Tian of NIMH, NIH
for genotyping and mouse brain dissections and Dr. Wei Tan of NCI, NIH
for original EF372273 construct synthesis.
NR 98
TC 3
Z9 3
U1 6
U2 12
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 27
PY 2016
VL 36
IS 17
BP 4859
EP 4875
DI 10.1523/JNEUROSCI.4632-15.2016
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA DK7UF
UT WOS:000375130500018
PM 27122041
ER
PT J
AU Avella, MA
Baibakov, BA
Jimenez-Movilla, M
Sadusky, AB
Dean, J
AF Avella, Matteo A.
Baibakov, Boris A.
Jimenez-Movilla, Maria
Sadusky, Anna Burkart
Dean, Jurrien
TI ZP2 peptide beads select human sperm in vitro, decoy mouse sperm in
vivo, and provide reversible contraception
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ZONA-PELLUCIDA PROTEIN; ACROSOME REACTION; TRANSGENIC MICE; SULFATED
GLYCOPROTEIN; GAMETE RECOGNITION; SPERMATOZOA; SPERMATOGENESIS;
FERTILIZATION; INHIBITION; MORPHOLOGY
AB Gamete recognition in the female reproductive tract occurs at the surface of the zona pellucida surrounding ovulated eggs. The acellular zona matrix is composed of three (mouse) or four (human) proteins (ZP1 to ZP4), and the amino terminus of ZP2 is the primary sperm-binding ligand. Mouse and human sperm bind, respectively, to recombinant moZP2(35-149) and huZP2(39-154) peptides attached to agarose beads. Mouse ZP2 peptide beads markedly inhibited fertilization of ovulated mouse eggs inseminated in vitro and incubated overnight. Similarly, human ZP2 peptide beads prevented sperm binding and penetration of transgenic ZP2(Rescue) zonae pellucidae, in which human ZP2 replaced mouse ZP2. When mouse ZP2 peptide beads were transcervically deposited into the uterus, there was no change in mating behavior and copulatory plugs were present, but bound sperm did not progress into the oviduct and female mice were infertile. On average, contraception lasted > 10 estrus cycles but was reversible with no detectable pathology in the reproductive tract. Despite the long-term contraceptive effect, initial sperm binding to the peptide beads was reversible in vitro. We exploited this observation to select human sperm that were better able to penetrate the zonae of human ZP2(Rescue) eggs, and the approach holds promise for identifying superior sperm for human assisted reproductive technologies (ART). We conclude that the amino-terminal ZP2 peptide supports sperm binding, which is initially reversible but, with time, becomes irreversible. Short-term, reversible binding may be useful in selecting sperm for ART, and long-term binding decoys sperm and results in effective contraception in mice.
C1 [Avella, Matteo A.; Baibakov, Boris A.; Sadusky, Anna Burkart; Dean, Jurrien] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jimenez-Movilla, Maria] Univ Murcia, Sch Med, Dept Cell Biol & Histol, IMIB, E-30100 Murcia, Spain.
RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jurriend@helix.nih.gov
RI Jimenez-Movilla, Maria/I-1004-2015
OI Jimenez-Movilla, Maria/0000-0002-1572-8219
FU Intramural Research Program of NIDDK, NIH; Fundacion Seneca-Agencia y
Tecnologia de la Region de Murcia (Jovenes Lideres en Investigacion)
FX The research was supported by the Intramural Research Program of NIDDK,
NIH. The contributions of M.J.-M. were supported by the Fundacion
Seneca-Agencia y Tecnologia de la Region de Murcia (Jovenes Lideres en
Investigacion).
NR 38
TC 3
Z9 3
U1 5
U2 10
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 27
PY 2016
VL 8
IS 336
AR 336ra60
DI 10.1126/scitranslmed.aad9946
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DK3QW
UT WOS:000374833500005
PM 27122613
ER
PT J
AU Liput, DJ
Lu, V
Davis, MI
Puhl, HL
Ikeda, SR
AF Liput, Daniel J.
Lu, Van B.
Davis, Margaret I.
Puhl, Henry L.
Ikeda, Stephen R.
TI Rem2, a member of the RGK family of small GTPases, is enriched in nuclei
of the basal ganglia
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DEPENDENT CALCIUM-CHANNELS; CENTRAL-NERVOUS-SYSTEM; GTP-BINDING
PROTEINS; DENDRITIC COMPLEXITY; CELL-SHAPE; NEURONS; EXPRESSION;
NEOSTRIATUM; STRIATUM; PHOSPHORYLATION
AB Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology.
C1 [Liput, Daniel J.; Lu, Van B.; Puhl, Henry L.; Ikeda, Stephen R.] NIAAA, Labs Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Davis, Margaret I.] NIAAA, Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
RP Ikeda, SR (reprint author), NIAAA, Labs Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM sikeda@mail.nih.gov
FU National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, Division of Intramural Clinical and Biological Research
(DICBR)
FX This work was supported by the National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism, Division of Intramural
Clinical and Biological Research (DICBR).
NR 42
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 27
PY 2016
VL 6
AR 25137
DI 10.1038/srep25137
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK4AP
UT WOS:000374858900002
PM 27118437
ER
PT J
AU Nagaya, T
Nakamura, Y
Sato, K
Zhang, YF
Ni, M
Choyke, PL
Ho, M
Kobayashi, H
AF Nagaya, Tadanobu
Nakamura, Yuko
Sato, Kazuhide
Zhang, Yi-Fan
Ni, Min
Choyke, Peter L.
Ho, Mitchell
Kobayashi, Hisataka
TI Near infrared photoimmunotherapy with an anti-mesothelin antibody
SO ONCOTARGET
LA English
DT Article
DE near infrared photoimmunotherapy; mesothelin; hYP218; humanized
monoclonal antibodies; molecular imaging
ID FLUORESCENCE-GUIDED SURGERY; PANCREATIC-CANCER; ENHANCED PERMEABILITY;
PLEURAL MESOTHELIOMA; POTENTIATING FACTOR; SERUM MESOTHELIN;
OVARIAN-CANCER; TUMOR-MODEL; THERAPY; ADENOCARCINOMAS
AB Near Infrared-Photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs an antibody-photon absorber conjugate (APC). When the APC attaches to its target cell and is exposed to NIR light, highly selective cell killing is observed. NIR-PIT has been demonstrated with a limited number of antibodies. Mesothelin is overexpressed in several malignancies and is emerging as a therapeutic target. A recently humanized antibody (hYP218) has been generated against mesothelin that demonstrates high affinity binding. Here, we describe the efficacy of NIR-PIT, using hYP218 as the antibody within the APC to target a mesothelin expressing A431/H9 cell. The hYP218 antibody was conjugated to a photo-absorber, IR700 and incubated with the cells. The hYP218-IR700 showed specific binding to cells and cell-specific killing was observed in vitro. After implanting A431/H9 cells in an athymic nude mouse, tumor-bearing mice were treated with the following regimen of NIR-PIT; 100 mu g of hYP218-IR700 i.v., NIR light was administered at 50 J/cm(2) on day 1 after injection and 100 J/cm(2) of light on day 2 after injection. The hYP218-IR700 showed high tumor accumulation and a high tumor-background ratio (TBR). Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups (p < 0.001), and significantly prolonged survival (p < 0.0001 vs other groups). Thus, the new anti-mesothelin antibody, hYP218, is suitable as an antibody-drug conjugate for NIR-PIT. Furthermore, NIR-PIT with hYP218-IR700 is a promising candidate for the treatment of mesothelin-expressing tumors that could be readily translated to humans.
C1 [Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Yi-Fan; Ni, Min; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
OI Zhang, Yifan/0000-0002-0629-0200
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research [ZIA BC011513, Z01
BC010891, ZIA BC010891]; JSPS; (China) Jiangsu Government Scholarship
for Overseas Studies
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (ZIA BC011513, Z01 BC010891, ZIA BC010891). Kazuhide
Sato is supported with JSPS Research Fellowship for Japanese Biomedical
and Behavioral Researchers at NIH. Min Ni is supported with the (China)
Jiangsu Government Scholarship for Overseas Studies. We thank Dr. Bryan
Fleming (NCI) for editorial assistance.
NR 38
TC 5
Z9 5
U1 9
U2 10
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 26
PY 2016
VL 7
IS 17
BP 23361
EP 23369
DI 10.18632/oncotarget.8025
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO3UB
UT WOS:000377706200030
PM 26981775
ER
PT J
AU Kwilas, AR
Ardiani, A
Gameiro, SR
Richards, J
Hall, AB
Hodge, JW
AF Kwilas, Anna R.
Ardiani, Andressa
Gameiro, Sofia R.
Richards, Jacob
Hall, Ashley B.
Hodge, James W.
TI Androgen deprivation therapy sensitizes triple negative breast cancer
cells to immune-mediated lysis through androgen receptor independent
modulation of osteoprotegerin
SO ONCOTARGET
LA English
DT Article
DE enzalutamide; abiraterone; androgen deprivation therapy; TNBC;
immunogenic modulation
ID TRAIL-INDUCED APOPTOSIS; PROSTATE-CANCER; TUMOR-CELLS; COMBINATION
THERAPY; IMPROVES SURVIVAL; LIGAND TRAIL; IN-VITRO; EXPRESSION; OPG;
PATHWAY
AB Among breast cancer types, triple-negative breast cancer (TNBC) has the fewest treatment options and the lowest 5-year survival rate. Androgen receptor (AR) inhibition has displayed efficacy against breast cancer preclinically and is currently being examined clinically in AR positive TNBC patients. Androgen deprivation has been shown to induce immunogenic modulation; the alteration of tumor cell phenotype resulting in increased sensitivity to immune-mediated killing. We evaluated the ability of AR inhibition to reduce the growth and improve the immune-mediated killing of breast cancer cells with differing expression of the estrogen receptor and AR. While AR expression was required for the growth inhibitory effects of enzalutamide on breast cancer cells, both enzalutamide and abiraterone improved the sensitivity of breast cancer cells to immune-mediated lysis independent of detectable AR expression. This increase in sensitivity was linked to an increase in cell surface tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression as well as a significant reduction in the expression of osteoprotegerin (OPG). The reduction in OPG was further examined and found to be critical for the increase in sensitivity of AR-TNBC cells to immune-mediated killing. The data presented herein further support the use of AR inhibition therapy in the AR+ TNBC setting. These data, however, also support the consideration of AR inhibition therapy for the treatment of AR-TNBC, especially in combination with cancer immunotherapy, providing a potential novel therapeutic option for select patients.
C1 [Kwilas, Anna R.; Ardiani, Andressa; Gameiro, Sofia R.; Richards, Jacob; Hall, Ashley B.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 55
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 26
PY 2016
VL 7
IS 17
BP 23498
EP 23511
DI 10.18632/oncotarget.8274
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO3UB
UT WOS:000377706200040
PM 27015557
ER
PT J
AU Tanigawa, S
Taguchi, A
Sharma, N
Perantoni, AO
Nishinakamura, R
AF Tanigawa, Shunsuke
Taguchi, Atsuhiro
Sharma, Nirmala
Perantoni, Alan O.
Nishinakamura, Ryuichi
TI Selective In Vitro Propagation of Nephron Progenitors Derived from
Embryos and Pluripotent Stem Cells
SO CELL REPORTS
LA English
DT Article
ID SELF-RENEWAL; MOUSE KIDNEY; NEPHROGENESIS; MAINTAIN; SIX2;
DIFFERENTIATION; ORGANOGENESIS; MESENCHYME; INDUCTION; ORGANOIDS
AB Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, in mice, the progenitors terminally differentiate shortly after birth. Here, we report a method for selectively expanding nephron progenitors in vitro in an undifferentiated state. Combinatorial and concentration-dependent stimulation with LIF, FGF2/9, BMP7, and a WNT agonist is critical for expansion. The purified progenitors proliferated beyond the physiological limits observed in vivo, both for cell numbers and lifespan. Neonatal progenitors were maintained for a week, while progenitors from embryonic day 11.5 expanded 1,800-fold for nearly 20 days and still reconstituted 3D nephrons containing glomeruli and renal tubules. Furthermore, progenitors generated from mouse embryonic stem cells and human induced pluripotent cells could be expanded with retained nephron-forming potential. Thus, we have established in vitro conditions for promoting the propagation of nephron progenitors, which will be essential for dissecting the mechanisms of kidney organogenesis and for regenerative medicine.
C1 [Tanigawa, Shunsuke; Taguchi, Atsuhiro; Nishinakamura, Ryuichi] Kumamoto Univ, Inst Mol Embryol & Genet, Dept Kidney Dev, Kumamoto 8600811, Japan.
[Sharma, Nirmala; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, NIH, Ft Detrick, MD 21702 USA.
RP Nishinakamura, R (reprint author), Kumamoto Univ, Inst Mol Embryol & Genet, Dept Kidney Dev, Kumamoto 8600811, Japan.
EM ryuichi@kumamoto-u.ac.jp
OI Taguchi, Atsuhiro/0000-0003-1741-2987
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan [26860640, 26253051]; program for leading graduate schools, HIGO
program, Kumamoto University
FX We thank Tomoko Ohmori and Sayoko Fujimura for their technical
assistance. This study was supported, in part, by grants KAKENHI
26860640 to S.T. and 26253051 to R.N. from the Ministry of Education,
Culture, Sports, Science and Technology (MEXT) of Japan. This work was
also supported, in part, by the program for leading graduate schools,
HIGO program, Kumamoto University.
NR 41
TC 4
Z9 4
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD APR 26
PY 2016
VL 15
IS 4
BP 801
EP 813
DI 10.1016/j.celrep.2016.03.076
PG 13
WC Cell Biology
SC Cell Biology
GA DK2FS
UT WOS:000374730600013
ER
PT J
AU Wang, XT
Campbell, MR
Lacher, SE
Cho, HY
Wan, M
Crowl, CL
Chorley, BN
Bond, GL
Kleeberger, SR
Slattery, M
Bell, DA
AF Wang, Xuting
Campbell, Michelle R.
Lacher, Sarah E.
Cho, Hye-Youn
Wan, Ma
Crowl, Christopher L.
Chorley, Brian N.
Bond, Gareth L.
Kleeberger, Steven R.
Slattery, Matthew
Bell, Douglas A.
TI A Polymorphic Antioxidant Response Element Links NRF2/sMAF Binding to
Enhanced MAPT Expression and Reduced Risk of Parkinsonian Disorders
SO CELL REPORTS
LA English
DT Article
ID GENE-EXPRESSION; HUMAN GENOME; NEURODEGENERATIVE DISEASES;
ALZHEIMERS-DISEASE; CONSENSUS SEQUENCE; COMMON VARIANTS; IDENTIFICATION;
NRF2; DNA; TAU
AB The NRF2/sMAF protein complex regulates the oxidative stress response by occupying cis-acting enhancers containing an antioxidant response element (ARE). Integrating genome-wide maps of NRF2/sMAF occupancy with disease-susceptibility loci, we discovered eight polymorphic AREs linked to 14 highly ranked disease-risk SNPs in individuals of European ancestry. Among these SNPs was rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple experiments and its strong-binding allele associated with higher mRNA levels in cell lines and human brain tissue. Induction of MAPT transcription by NRF2 was confirmed using a human neuroblastoma cell line and a Nrf2-deficient mouse model. Most importantly, rs242561 displayed complete linkage disequilibrium with a highly protective allele identified in multiple GWASs of progressive supranuclear palsy, Parkinson's disease, and corticobasal degeneration. These observations suggest a potential role for NRF2/sMAF in tauopathies and a possible role for NRF2 pathway activators in disease prevention.
C1 [Wang, Xuting; Campbell, Michelle R.; Wan, Ma; Crowl, Christopher L.; Chorley, Brian N.; Bell, Douglas A.] Natl Inst Environm Hlth Sci, Environm Genom Sect, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Lacher, Sarah E.; Slattery, Matthew] Univ Minnesota, Sch Med, Dept Biomed Sci, Duluth, MN 55812 USA.
[Lacher, Sarah E.; Slattery, Matthew] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA.
[Cho, Hye-Youn; Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bond, Gareth L.] Univ Oxford, Nuffield Dept Clin Med, Ludwig Inst Canc Res, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
[Chorley, Brian N.] US Environm Protect Agcy, Res Triangle Pk, NC 27709 USA.
RP Wang, XT; Bell, DA (reprint author), Natl Inst Environm Hlth Sci, Environm Genom Sect, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM wang21@niehs.nih.gov; bell1@niehs.nih.gov
OI Wang, Xuting/0000-0001-6781-8008
FU Intramural Research Program of National Institute of Environmental
Health Sciences, NIH [Z01ES100475, Z01ES46008]; University of Minnesota
Foundation; Ludwig Institute for Cancer Research
FX This work was funded by the Intramural Research Program of National
Institute of Environmental Health Sciences, NIH (projects: Z01ES100475
and Z01ES46008), the University of Minnesota Foundation (to M.S.), and
the Ludwig Institute for Cancer Research (to G.L.B.). The authors would
like to acknowledge Dr. Shuangshuang Dai for Linux computing support;
NIEHS Epigenomics Core; NIEHS Animal Facility Core; and Dr. Jean Harry,
NIEHS, for technical advice and useful comments on the manuscript.
NR 53
TC 3
Z9 3
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD APR 26
PY 2016
VL 15
IS 4
BP 830
EP 842
DI 10.1016/j.celrep.2016.03.068
PG 13
WC Cell Biology
SC Cell Biology
GA DK2FS
UT WOS:000374730600015
ER
PT J
AU Hong, CS
Yang, CZ
Zhuang, ZP
AF Hong, Christopher S.
Yang, Chunzhang
Zhuang, Zhengping
TI Application of Peptide Nucleic Acid-based Assays Toward Detection of
Somatic Mosaicism
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
DE gene sequencing; oligonucleotide; peptide nucleic acid; polymerase chain
reaction; somatic mosaicism
ID CELL LUNG-CANCER; MUTATIONS; NEUROFIBROMATOSIS; DISEASE; CLAMP; GENE;
PCR; DNA
AB Peptide nucleic acids (PNAs) are synthetic oligonucleotides with many applications. Compared with DNA, PNAs bind their complementary DNA strand with higher specificity and strength, an attribute that can make it an effective polymerase chain reaction clamp. A growing body of work has demonstrated the utility of PNAs in detecting low levels of mutant DNA, particularly in the detection of circulating mutated tumor cells in the peripheral blood. The PNA-based assay has greater sensitivity than direct sequencing and is significantly more affordable and rapid than next-generation deep sequencing. We have previously demonstrated that PNAs can successfully detect somatic mosaicism in patients with suspected disease phenotypes. In this report, we detail our methodology behind PNA design and application. We describe our protocol for optimizing the PNA for sequencing use and for determining the sensitivity of the PNA-based assay. Lastly, we discuss the potential applications of our assay for future laboratory and clinical purposes and highlight the role of PNAs in the detection of somatic mosaicism.
C1 [Hong, Christopher S.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Yang, Chunzhang] NCI, Neurooncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zhuang, ZP (reprint author), 10 Ctr Dr,Room 3D20, Bethesda, MD 20892 USA.
EM zhuangp@ninds.nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke (NINDS) at the National Institutes of Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (NINDS) at the
National Institutes of Health (NIH).
NR 31
TC 0
Z9 0
U1 5
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD APR 26
PY 2016
VL 5
AR e314
DI 10.1038/mtna.2016.22
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DK2JS
UT WOS:000374741400001
PM 27115839
ER
PT J
AU Eddy, EM
Chen, LY
AF Eddy, Edward M.
Chen, Liang-Yu
TI Role of GDNF from peritubular myoid cells in the testis stem cell niche
REPLY
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Eddy, Edward M.; Chen, Liang-Yu] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
[Chen, Liang-Yu] VA San Diego Med Ctr, San Diego, CA 92161 USA.
RP Eddy, EM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 26
PY 2016
VL 113
IS 17
BP E2353
EP E2353
DI 10.1073/pnas.1603478113
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK2MK
UT WOS:000374748400004
PM 27044114
ER
PT J
AU Sadaoka, T
Depledge, DP
Rajbhandari, L
Venkatesan, A
Breuer, J
Cohen, JI
AF Sadaoka, Tomohiko
Depledge, Daniel P.
Rajbhandari, Labchan
Venkatesan, Arun
Breuer, Judith
Cohen, Jeffrey I.
TI In vitro system using human neurons demonstrates that varicella-zoster
vaccine virus is impaired for reactivation, but not latency
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE varicella-zoster virus; varicella vaccine; reactivation; latency;
herpesvirus
ID HERPES-ZOSTER; RNA-SEQ; MICROGLIAL PHAGOCYTOSIS; DEGENERATING AXONS;
SKIN XENOGRAFTS; PARENTAL VIRUS; UNITED-STATES; LONG-TERM; CHILDREN; DNA
AB Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. The mechanism of how the virus establishes and maintains latency and how it reactivates is poorly understood, largely due to the lack of robust models. We found that axonal infection of neurons derived from hESCs in a microfluidic device with cell-free parental Oka (POka) VZV resulted in latent infection with inability to detect several viral mRNAs by reverse transcriptase-quantitative PCR, no production of infectious virus, and maintenance of the viral DNA genome in endless configuration, consistent with an episome configuration. With deep sequencing, however, multiple viral mRNAs were detected. Treatment of the latently infected neurons with Ab to NGF resulted in production of infectious virus in about 25% of the latently infected cultures. Axonal infection of neurons with vaccine Oka (VOka) VZV resulted in a latent infection similar to infection with POka; however, in contrast to POka, VOka-infected neurons were markedly impaired for reactivation after treatment with Ab to NGF. In addition, viral transcription was markedly reduced in neurons latently infected with VOka compared with POka. Our in vitro system recapitulates both VZV latency and reactivation in vivo and may be used to study viral vaccines for their ability to establish latency and reactivate.
C1 [Sadaoka, Tomohiko; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Depledge, Daniel P.; Breuer, Judith] UCL, MRC Ctr Med Mol Virol, Div Infect & Immun, Mortimer St, London WC1E 6BT, England.
[Rajbhandari, Labchan; Venkatesan, Arun] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Div Neuroimmunol & Neuroinfect Dis,Dept Neurol, Baltimore, MD 21287 USA.
[Sadaoka, Tomohiko] Kobe Univ, Div Clin Virol, Ctr Infect Dis, Grad Sch Med,Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
OI sadaoka, tomohiko/0000-0001-7951-6904
FU intramural research program of the National Institute of Allergy and
Infectious Diseases; Japan Herpesvirus Infections Forum; New
Investigator Award from Medical Research Foundation [UK Medical Research
Council (MRC)]; UCL/UCLH Biomedical Research Centre (BRC); Maryland Stem
Cell Research Fund
FX This work was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases. T.S. was
supported by the Japan Herpesvirus Infections Forum. D.P.D. is supported
by a New Investigator Award from the Medical Research Foundation [UK
Medical Research Council (MRC)]. J.B. was partially funded by the
UCL/UCLH Biomedical Research Centre (BRC). A.V. received funding from
the Maryland Stem Cell Research Fund. We acknowledge support from the
MRC and BRC for the UCL/UCLH Pathogen Sequencing Pipeline.
NR 57
TC 1
Z9 1
U1 5
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 26
PY 2016
VL 113
IS 17
BP E2403
EP E2412
DI 10.1073/pnas.1522575113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK2MK
UT WOS:000374748400011
PM 27078099
ER
PT J
AU Jaszczur, M
Bertram, JG
Robinson, A
van Oijen, AM
Woodgate, R
Cox, MM
Goodman, MF
AF Jaszczur, Malgorzata
Bertram, Jeffrey G.
Robinson, Andrew
van Oijen, Antoine M.
Woodgate, Roger
Cox, Michael M.
Goodman, Myron F.
TI Mutations for Worse or Better: Low-Fidelity DNA Synthesis by SOS DNA
Polymerase V Is a Tightly Regulated Double-Edged Sword
SO BIOCHEMISTRY
LA English
DT Article
ID SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; RECA PROTEIN; MUTAGENESIS
PROTEIN; UV MUTAGENESIS; Y-FAMILY; TRANSLESION SYNTHESIS;
ULTRAVIOLET-LIGHT; III HOLOENZYME; UMUD
AB 1953, the year of Watson and Crick, bore witness to a less acclaimed yet highly influential discovery. Jean Weigle demonstrated that upon infection of Escherichia coli, 2 phage deactivated by UV radiation, and thus unable to form progeny, could be reactivated by irradiation of the bacterial host. Evelyn Witkin and Miroslav Radman later revealed the presence of the SOS regulon. The more than 40 regulon genes are repressed by LexA protein and induced by the coproteolytic cleavage of LexA, catalyzed by RecA protein bound to single stranded DNA, the RecA* nucleoprotein filament. Several SOS-induced proteins are engaged in repairing both cellular and extracellular damaged DNA. There's no "free lunch", however, because error-free repair is accompanied by error-prone translesion DNA synthesis (TLS), involving E. coli DNA polymerase V (UmuD'C-2) and RecA*. This review describes the biochemical mechanisms of pol V-mediated TLS. pol V is active only as a mutasomal complex, pol V Mut = UmuD'C-2-RecA-ATP. RecA* donates a single RecA subunit to pol V. We highlight three recent insights. (1) pol V Mut has an intrinsic DNA dependent ATPase activity that governs polymerase binding and dissociation from DNA. (2) Active and inactive states of pol V Mut are determined at least in part by the distinct interactions between RecA and UmuC. (3) pol V is activated by RecA*, not at a blocked replisome, but at the inner cell membrane.
C1 [Jaszczur, Malgorzata; Bertram, Jeffrey G.; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Robinson, Andrew; van Oijen, Antoine M.] Univ Wollongong, Sch Chem, Wollongong, NSW, Australia.
[Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Rockville, MD 20850 USA.
[Cox, Michael M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
[Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.; Goodman, MF (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
EM mgoodman@usc.edu
OI Robinson, Andrew/0000-0002-3544-0976; van Oijen,
Antoine/0000-0002-1794-5161
FU National Institutes of Health [ES012259, GM21422, GM32335]; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development/National Institutes of Health Intramural Research Program;
Netherlands Organization for Scientific Research (NWO) [Vici
680-47-607]; European Research Council (ERC) [281098]
FX This work was supported by National Institutes of Health grants to
M.F.G. (ES012259 and GM21422) and M.M.C. (GM32335), funds from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development/National Institutes of Health Intramural Research Program to
R.W., and funds from The Netherlands Organization for Scientific
Research (NWO; Vici 680-47-607) and the European Research Council (ERC
Starting 281098) to A.M.v.O.
NR 72
TC 0
Z9 0
U1 4
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 26
PY 2016
VL 55
IS 16
BP 2309
EP 2318
DI 10.1021/acs.biochem.6b00117
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK9IT
UT WOS:000375244800003
PM 27043933
ER
PT J
AU Park, JH
Sayer, JM
Aniana, A
Yu, XX
Weber, IT
Harrison, RW
Louis, JM
AF Park, Joon H.
Sayer, Jane M.
Aniana, Annie
Yu, Xiaxia
Weber, Irene T.
Harrison, Robert W.
Louis, John M.
TI Binding of Clinical Inhibitors to a Model Precursor of a Rationally
Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than
That to the Released Mature Enzyme
SO BIOCHEMISTRY
LA English
DT Article
ID VIRUS TYPE-1 PROTEASE; DRUG-RESISTANCE; NMR-SPECTROSCOPY; 20 MUTATIONS;
GAG; DYNAMICS; KINETICS; MECHANISM; DARUNAVIR; MONOMER
AB We have systematically validated the activity and inhibition of a HIV-1 protease (PR) variant bearing 17 mutations (PRS17), selected to represent high resistance by machine learning on genotype phenotype data. Three of five mutations in PRS17 correlating with major drug resistance, M46L, G48V, and V82S, and five of 11 natural variations differ from the mutations in two clinically derived extreme mutants, PR20 and PR22 bearing 19 and 22 mutations, respectively. PRS17, which forms a stable dimer (<10 nM), is similar to 10- and 2-fold less efficient in processing the Gag polyprotein than the wild type and PR20, respectively, but maintains the same cleavage order. Isolation of a model precursor of PRS17 flanked by the 56-amino acid transframe region (TFP-p6pol) at its N-terminus, which is impossible upon expression of an analogous PR20 precursor, allowed systematic comparison of inhibition of TFP-p6pol-PRS17 and mature PRS17. Resistance of PRS17 to eight protease inhibitors (PIs) relative to PR (K-i) increases by 1.5-5 orders of magnitude from 0.01 to 8.4 mu M. Amprenavir, darunavir, atazanavir, and lopinavir, the most effective of the eight PIs, inhibit precursor autoprocessing at the p6pol/PR site with IC50 values ranging from similar to 7.5 to 60 mu M. Thus, this process, crucial for stable dimer formation, shows inhibition similar to 200-800-fold weaker than that of the mature PRS17. TFP/p6pol cleavage, which occurs faster, is inhibited even more weakly by all PIs except darunavir (IC50 = 15 mu M); amprenavir shows a 2-fold increase in IC50 (similar to 15 mu M), and atazanavir and lopinavir show increased IC50 values of >42 and >70 mu M, respectively.
C1 [Park, Joon H.; Sayer, Jane M.; Aniana, Annie; Louis, John M.] NIDDK, Chem Phys Lab, NIH, Dept Hlth & Human Serv, Bldg 2, Bethesda, MD 20892 USA.
[Yu, Xiaxia; Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
[Weber, Irene T.] Georgia State Univ, Dept Biol, POB 4010, Atlanta, GA 30303 USA.
RP Louis, JM (reprint author), NIDDK, LCP, NIH, Bldg 5,Room B2-29, Bethesda, MD 20892 USA.
EM johnl@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (NIH); Intramural AIDS-Targeted Program of
the Office of the Director, NIH, National Institutes of Health
[GM062920]; Georgia State University Molecular Basis of Disease Program
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (NIH), and the Intramural AIDS-Targeted
Program of the Office of the Director, NIH, National Institutes of
Health Grant GM062920 (I.T.W. and R.W.H.), and a fellowship from the
Georgia State University Molecular Basis of Disease Program (X.Y.).
NR 50
TC 2
Z9 2
U1 3
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 26
PY 2016
VL 55
IS 16
BP 2390
EP 2400
DI 10.1021/acs.biochem.6b00012
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK9IT
UT WOS:000375244800010
PM 27039930
ER
PT J
AU Delling, FN
Rong, J
Larson, MG
Lehman, B
Fuller, D
Osypiuk, E
Stantchev, P
Hackman, B
Manning, WJ
Benjamin, EJ
Levine, RA
Vasan, RS
AF Delling, Francesca N.
Rong, Jian
Larson, Martin G.
Lehman, Birgitta
Fuller, Deborah
Osypiuk, Ewa
Stantchev, Plamen
Hackman, Brianne
Manning, Warren J.
Benjamin, Emelia J.
Levine, Robert A.
Vasan, Ramachandran S.
TI Evolution of Mitral Valve Prolapse: Insights From the Framingham Heart
Study
SO CIRCULATION
LA English
DT Article
DE echocardiography; epidemiology; mitral valve
ID NATURAL-HISTORY; VENA CONTRACTA; REGURGITATION; PROGRESSION; DIAGNOSIS;
COMMUNITY; SEVERITY; DETERMINANTS; ASSOCIATION; PREVALENCE
AB Background Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking.
Methods and Results We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 5711 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height 5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05).
Conclusions NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression.
C1 [Delling, Francesca N.; Rong, Jian; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA.
[Delling, Francesca N.; Rong, Jian; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Delling, Francesca N.; Fuller, Deborah; Hackman, Brianne] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc,Sch Med, Boston, MA 02215 USA.
[Rong, Jian] Boston Univ, Sch Med, Dept Med, Neurol Sect, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiol, Sch Med, Boston, MA 02215 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02215 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA.
RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 330 Brookline Ave,E-SH-458, Boston, MA 02215 USA.
EM fdelling@bidmc.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU Founders Affiliate American Heart Association Clinical Research Program;
National Heart, Lung and Blood Institute Framingham Heart Study
[N01-HC-25195, HHSN268201500001I, R01HL080124, RO1HL0107385,
2R01HL092577, 1R01HL128914, K23HL116652]
FX This work was supported by the Founders Affiliate American Heart
Association Clinical Research Program (to Dr Delling), and by the
National Heart, Lung and Blood Institute Framingham Heart Study Contract
No. N01-HC-25195 and HHSN268201500001I (both to Dr Vasan), and research
grants R01HL080124, RO1HL0107385 (to Dr Vasan), 2R01HL092577,
1R01HL128914 (to Dr Benjamin), and K23HL116652 (to Dr Delling).
NR 31
TC 2
Z9 3
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD APR 26
PY 2016
VL 133
IS 17
BP 1688
EP 1695
DI 10.1161/CIRCULATIONAHA.115.020621
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DK6QI
UT WOS:000375049200012
PM 27006478
ER
PT J
AU Kaushal, M
Byrnes, C
Khademian, Z
Duncan, N
Luban, NLC
Miller, JL
Fasano, RM
Meier, ER
AF Kaushal, Megha
Byrnes, Colleen
Khademian, Zarir
Duncan, Natalie
Luban, Naomi L. C.
Miller, Jeffery L.
Fasano, Ross M.
Meier, Emily Riehm
TI Examination of Reticulocytosis among Chronically Transfused Children
with Sickle Cell Anemia
SO PLOS ONE
LA English
DT Article
ID SILENT CEREBRAL INFARCTS; RED-CELL; CEREBROVASCULAR ACCIDENTS;
HYDROXYUREA SWITCH; CNS INFARCTION; DISEASE; ADHESION; STROKE; BLOOD;
RISK
AB Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 +/- 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) - vasculopathy had significantly higher mean ARC prior to initiating CTT compared to 14 subjects without MRA-vasculopathy (427.6 +/- 109.0 K/mu l vs. 324.8 +/- 109.2 K/mu l, p<0.05). No significant differences in hemoglobin or percentage sickle hemoglobin (HbS) were noted between the two groups at baseline. Reticulocyte phenotyping further demonstrated that the percentages of circulating immature [CD36(+), CD71(+)] reticulocytes positively correlated with ARC in both groups. During the first year of CTT, neither group had significant reductions in ARC. Among this group of children with SCA, cerebrovasculopathy on MRA at initiation of CTT was associated with increased reticulocytosis, which was not reduced after 12 months of transfusions.
C1 [Kaushal, Megha; Byrnes, Colleen; Miller, Jeffery L.; Meier, Emily Riehm] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Kaushal, Megha; Luban, Naomi L. C.; Fasano, Ross M.; Meier, Emily Riehm] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Washington, DC USA.
[Khademian, Zarir] Childrens Natl Hlth Syst, Div Diagnost Imaging & Radiol, Washington, DC USA.
[Kaushal, Megha; Luban, Naomi L. C.; Fasano, Ross M.; Meier, Emily Riehm] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA.
[Duncan, Natalie; Meier, Emily Riehm] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA.
[Fasano, Ross M.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Ctr Transfus & Cellular Therapies, Atlanta, GA 30322 USA.
RP Meier, ER (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.; Meier, ER (reprint author), Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Washington, DC USA.; Meier, ER (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA.; Meier, ER (reprint author), Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA.
EM emeier@ihtc.org
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart Lung and Blood Institute
[HL110841]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and a
T32 from National Heart Lung and Blood Institute [HL110841]. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 43
TC 0
Z9 0
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 26
PY 2016
VL 11
IS 4
AR e0153244
DI 10.1371/journal.pone.0153244
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK5QB
UT WOS:000374973600017
PM 27116614
ER
PT J
AU Tomasi, D
Shokri-Kojori, E
Volkow, ND
AF Tomasi, D.
Shokri-Kojori, E.
Volkow, N. D.
TI Temporal Changes in Local Functional Connectivity Density Reflect the
Temporal Variability of the Amplitude of Low Frequency Fluctuations in
Gray Matter
SO PLOS ONE
LA English
DT Article
ID GLOBAL SIGNAL REGRESSION; HUMAN CONNECTOME PROJECT; ANTI-CORRELATED
NETWORKS; RESTING-STATE FMRI; ALZHEIMERS-DISEASE; HUMAN BRAIN; CORTICAL
NETWORKS; DYNAMICS; SCHIZOPHRENIA; PATTERNS
AB Data-driven functional connectivity density (FCD) mapping is being increasingly utilized to assess brain connectomics at rest in the healthy brain and its disruption in neuropsychiatric diseases with the underlying assumption that the spatiotemporal hub distribution is stationary. However, recent studies show that functional connectivity is highly dynamic. Here we study the temporal variability of the local FCD (lFCD) at high spatiotemporal resolution (2-mm isotropic; 0.72s) using a sliding-window approach and 'resting-state' datasets from 40 healthy subjects collected under the Human Connectome Project. Prominent functional connectivity hubs in visual and posterior parietal cortices had pronounced temporal changes in local FCD. These dynamic patterns in the strength of the lFCD hubs occurred in cortical gray matter with high sensitivity (up to 85%) and specificity (> 85%) and showed high reproducibility (up to 72%) across sessions and high test-retest reliability (ICC(3,1) > 0.5). The temporal changes in lFCD predominantly occurred in medial occipitoparietal regions and were proportional to the strength of the connectivity hubs. The temporal variability of the lFCD was associated with the amplitude of the low frequency fluctuations (ALFF). Pure randomness did not account for the probability distribution of lFCD. Shannon entropy increased in proportion to the strength of the lFCD hubs suggesting high average flow of information per unit of time in the lFCD hubs, particularly in medial occipitoparietal regions. Thus, the higher dynamic range of the lFCD hubs is consistent with their role in the complex orchestration of interacting brain networks.
C1 [Tomasi, D.; Shokri-Kojori, E.; Volkow, N. D.] NIAAA, Bethesda, MD USA.
[Volkow, N. D.] NIDA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), NIAAA, Bethesda, MD USA.
EM dardo.tomasi@nih.gov
FU NIH [1U54MH091657]; McDonnell Center for Systems Neuroscience at
Washington University; National Institutes of Alcohol Abuse and
Alcoholism [Y1AA-3009]
FX Data were provided by the Human Connectome Project, WU-Minn Consortium (
Principal Investigators: David Van Essen and Kamil Ugurbil;
1U54MH091657) funded by the 16 NIH Institutes and Centers that support
the NIH Blueprint for Neuroscience Research and by the McDonnell Center
for Systems Neuroscience at Washington University. This work was
accomplished with support from the National Institutes of Alcohol Abuse
and Alcoholism (Y1AA-3009).
NR 62
TC 4
Z9 4
U1 5
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 26
PY 2016
VL 11
IS 4
AR e0154407
DI 10.1371/journal.pone.0154407
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK5QB
UT WOS:000374973600065
PM 27116610
ER
PT J
AU Wang, YN
Hu, M
Liu, Q
Qin, JX
Dai, YX
He, L
Li, TM
Zheng, B
Zhou, F
Yu, KW
Fang, JY
Liu, XY
Otto, M
Li, M
AF Wang, Yanan
Hu, Mo
Liu, Qian
Qin, Juanxiu
Dai, Yingxin
He, Lei
Li, Tianming
Zheng, Bing
Zhou, Fan
Yu, Kaiwen
Fang, Jingyuan
Liu, Xiaoyun
Otto, Michael
Li, Min
TI Role of the ESAT-6 secretion system in virulence of the emerging
community-associated Staphylococcus aureus lineage ST398
SO SCIENTIFIC REPORTS
LA English
DT Article
ID METHICILLIN-RESISTANT; INFECTIONS; EPIDEMIOLOGY; PATHOGENESIS;
PNEUMONIA; PROTEINS
AB Novel Staphylococcus aureus clones continue to emerge that cause infections in otherwise healthy people. One example is the sequence type (ST) 398 lineage, which we show here is increasing in importance as a significant cause of community-associated (CA) human infections in China. We have a profound lack of understanding about what determines the considerable virulence potential of such newly emerging clones. Information about the contribution to virulence of the more recently discovered ESAT-6 secretion system (ESS) has remained particularly scarce. The Chinese ST398 isolates exhibited significantly increased expression of ESS genes as compared to predominant hospital-associated clones, which we found is likely due to increased expression of the accessory gene regulator (Agr) system and control of ESS by Agr. Importantly, deletion of essB in ST398 resulted in significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models. Our results demonstrate a key function of ESS in promoting virulence and mechanisms of resistance to innate host defense in an important emerging CA-S. aureus lineage. They suggest that ESS has a so far underestimated role in promoting aggressive virulence and epidemiological success of S. aureus.
C1 [Wang, Yanan; Liu, Qian; Qin, Juanxiu; Dai, Yingxin; He, Lei; Li, Tianming; Zheng, Bing; Li, Min] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai 200127, Peoples R China.
[Hu, Mo; Zhou, Fan; Yu, Kaiwen; Liu, Xiaoyun] Peking Univ, Coll Chem & Mol Engn, Inst Analyt Chem, Beijing 100871, Peoples R China.
[Hu, Mo; Zhou, Fan; Yu, Kaiwen; Liu, Xiaoyun] Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr, Beijing 100871, Peoples R China.
[Fang, Jingyuan] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Div Gastroenterol & Hepatol, Shanghai 200127, Peoples R China.
[Fang, Jingyuan] Shanghai Inst Digest Dis, Shanghai 200127, Peoples R China.
[Otto, Michael] NIAID, Bacteriol Lab, Pathogen Mol Genet Sect, NIH, Bethesda, MD 20892 USA.
RP Li, M (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai 200127, Peoples R China.; Otto, M (reprint author), NIAID, Bacteriol Lab, Pathogen Mol Genet Sect, NIH, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov; ruth_limin@126.com
OI Otto, Michael/0000-0002-2222-4115
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Natural Science Foundation of China
[81322025, 81421001, 81371875]; Shanghai Shuguang Talent Project
[12SG03]; Shanghai Committee of Science and Technology, China
[14140901000, 15411960500]
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (M.O.), the
National Natural Science Foundation of China (grants 81322025, 81421001
and 81371875, M.L.), the Shanghai Shuguang Talent Project (grant 12SG03,
M.L.), and the Shanghai Committee of Science and Technology, China
(grants 14140901000, 15411960500, M.L.).
NR 30
TC 4
Z9 5
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 26
PY 2016
VL 6
AR 25163
DI 10.1038/srep25163
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK6WK
UT WOS:000375066100001
PM 27112266
ER
PT J
AU Gurvitz, M
Burns, KM
Brindis, R
Broberg, CS
Daniels, CJ
Fuller, SMPN
Honein, MA
Khairy, P
Kuehl, KS
Landzberg, MJ
Mahle, WT
Mann, DL
Marelli, A
Newburger, JW
Pearson, GD
Starling, RC
Tringali, GR
Valente, AM
Wu, JC
Califf, RM
AF Gurvitz, Michelle
Burns, Kristin M.
Brindis, Ralph
Broberg, Craig S.
Daniels, Curt J.
Fuller, Stephanie M. P. N.
Honein, Margaret A.
Khairy, Paul
Kuehl, Karen S.
Landzberg, Michael J.
Mahle, William T.
Mann, Douglas L.
Marelli, Ariane
Newburger, Jane W.
Pearson, Gail D.
Starling, Randall C.
Tringali, Glenn R.
Valente, Anne Marie
Wu, Joseph C.
Califf, Robert M.
TI Emerging Research Directions in Adult Congenital Heart Disease A Report
From an NHLBI/ACHA Working Group
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE congenital; heart defects; outcomes; pregnancy; single ventricle; sudden
cardiac death; tetralogy of Fallot
ID 2009 CONSENSUS CONFERENCE; SURGICALLY REPAIRED TETRALOGY; ARTERIAL
SWITCH OPERATION; AORTIC COARCTATION REPAIR; ACCESS RESEARCH TRIAL;
TERM-FOLLOW-UP; FONTAN PATIENTS; GENERAL-POPULATION; GREAT-ARTERIES;
UNITED-STATES
AB Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed > 85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy. (C) 2016 by the American College of Cardiology Foundation.
C1 [Gurvitz, Michelle; Landzberg, Michael J.; Valente, Anne Marie] Harvard Univ, Sch Med, Boston Adult Congenital Heart & Pulm Hypertens Pr, Boston Childrens Hosp, Boston, MA USA.
[Gurvitz, Michelle; Landzberg, Michael J.; Valente, Anne Marie] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Burns, Kristin M.; Pearson, Gail D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Brindis, Ralph] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Broberg, Craig S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Daniels, Curt J.] Ohio State Univ, Columbus, OH 43210 USA.
[Fuller, Stephanie M. P. N.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Honein, Margaret A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Khairy, Paul] Univ Montreal, Montreal, PQ, Canada.
[Kuehl, Karen S.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Mahle, William T.] Emory Univ, Sch Med, Atlanta, GA USA.
[Mann, Douglas L.] Washington Univ, St Louis, MO USA.
[Marelli, Ariane] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Newburger, Jane W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA.
[Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA.
[Tringali, Glenn R.] Adult Congenital Heart Assoc, Philadelphia, PA USA.
[Wu, Joseph C.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Califf, Robert M.] Duke Univ, Durham, NC USA.
RP Gurvitz, M (reprint author), Boston Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM Michelle.gurvitz@cardio.chboston.org
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland; Adult
Congenital Heart Association, Philadelphia, Pennsylvania
FX This research was supported by the National Heart, Lung, and Blood
Institute, Bethesda, Maryland, and the Adult Congenital Heart
Association, Philadelphia, Pennsylvania. The views and conclusions in
this report are those of the authors and do not necessarily represent
the official position of the National Institutes of Health or the
Centers for Disease Control and Prevention. The authors have reported
that they have no relationships relevant to the contents of this paper
to disclose. Thomas Bashore, MD, served as Guest Editor for this paper.
NR 66
TC 6
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 26
PY 2016
VL 67
IS 16
BP 1956
EP 1964
DI 10.1016/j.jacc.2016.01.062
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK1EG
UT WOS:000374654700012
PM 27102511
ER
PT J
AU Barnes, TD
Wozniak, DF
Gutierrez, J
Han, TU
Drayna, D
Holy, TE
AF Barnes, Terra D.
Wozniak, David F.
Gutierrez, Joanne
Han, Tae-Un
Drayna, Dennis
Holy, Timothy E.
TI A Mutation Associated with Stuttering Alters Mouse Pup Ultrasonic
Vocalizations
SO CURRENT BIOLOGY
LA English
DT Article
ID SPEECH; LANGUAGE; MICE; SEAGRASSES; DISORDERS; FREQUENCY; ECOSYSTEM;
DEFICITS; FLUENCY
AB A promising approach to understanding the mechanistic basis of speech is to study disorders that affect speech without compromising other cognitive or motor functions. Stuttering, also known as stammering, has been linked to mutations in the lysosomal enzyme-targeting pathway, but how this remarkably specific speech deficit arises from mutations in a family of general "cellular housekeeping" genes is unknown. To address this question, we asked whether a missense mutation associated with human stuttering causes vocal or other abnormalities in mice. We compared vocalizations from mice engineered to carry a mutation in the Gnptab (N-acetylglucosamine-1-phosphotransferase subunits alpha/beta) gene with wild-type littermates. We found significant differences in the vocalizations of pups with the human Gnptab stuttering mutation compared to littermate controls. Specifically, we found that mice with the mutation emitted fewer vocalizations per unit time and had longer pauses between vocalizations and that the entropy of the temporal sequence was significantly reduced. Furthermore, Gnptab missense mice were similar to wild-type mice on an extensive battery of non-vocal behaviors. We then used the same language-agnostic metrics for auditory signal analysis of human speech. We analyzed speech from people who stutter with mutations in this pathway and compared it to control speech and found abnormalities similar to those found in the mouse vocalizations. These data show that mutations in the lysosomal enzyme-targeting pathway produce highly specific effects in mouse pup vocalizations and establish the mouse as an attractive model for studying this disorder.
C1 [Barnes, Terra D.; Holy, Timothy E.] Washington Univ, Sch Med St Louis, Dept Neurosci, Campus Box 8108,660 S Euclid Ave, St Louis, MO 63110 USA.
[Wozniak, David F.] Washington Univ, Sch Med St Louis, Dept Psychiat, Campus Box 8134,660 S Euclid Ave, St Louis, MO 63110 USA.
[Wozniak, David F.] Washington Univ, Sch Med St Louis, Taylor Family Inst Innovat Psychiat Res, Campus Box 8108,660 S Euclid Ave, St Louis, MO 63110 USA.
[Gutierrez, Joanne; Han, Tae-Un; Drayna, Dennis] NIDCD, NIH, Bethesda, MD 20892 USA.
RP Barnes, TD (reprint author), Washington Univ, Sch Med St Louis, Dept Neurosci, Campus Box 8108,660 S Euclid Ave, St Louis, MO 63110 USA.
EM terra.barnes@gmail.com
FU NIH Director's Pioneer Award [DP1 OD006437]; Intellectual and
Developmental Disabilities Research Center grants [P30 HD062171, U54
HD087011]; NIDCD Intramural grant [Z1A-000046-15]
FX We thank the Hollins Communication Research Institute for assistance
with subject recruitment and stuttering diagnosis. We thank Peter
Rietzes of StutterTalk for help with speech samples from PWS. We thank
Grace Liao and Cassandra Roberts for help with vocal recordings of mice;
Wayne Barnes and Thanh Loan Nguyen for their help with mouse genotyping;
and Sara Conyers for her work involving the non-vocalization behavioral
testing. This work was supported by the NIH Director's Pioneer Award
(DP1 OD006437), Intellectual and Developmental Disabilities Research
Center grants (P30 HD062171; U54 HD087011), and NIDCD Intramural grant
Z1A-000046-15.
NR 48
TC 3
Z9 3
U1 2
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD APR 25
PY 2016
VL 26
IS 8
BP 1009
EP 1018
DI 10.1016/j.cub.2016.02.068
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DL0RG
UT WOS:000375339700018
ER
PT J
AU Cong, XM
Xu, WL
Janton, S
Henderson, WA
Matson, A
McGrath, JM
Maas, K
Graf, J
AF Cong, Xiaomei
Xu, Wanli
Janton, Susan
Henderson, Wendy A.
Matson, Adam
McGrath, Jacqueline M.
Maas, Kendra
Graf, Joerg
TI Gut Microbiome Developmental Patterns in Early Life of Preterm Infants:
Impacts of Feeding and Gender
SO PLOS ONE
LA English
DT Article
ID NEONATAL RESEARCH NETWORK; NECROTIZING ENTEROCOLITIS; INTESTINAL
MICROBIOTA; MILK OLIGOSACCHARIDES; OUTCOMES; AUTOIMMUNITY; LACTATION;
DIVERSITY; INFECTION; SEVERITY
AB Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and alpha-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixe-deffects models showed that postnatal days, feeding types and gender were associated with the a-diversity, p< 0.05-0.01. Male infants were found to begin with a low a-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.
C1 [Cong, Xiaomei; Xu, Wanli; McGrath, Jacqueline M.] Univ Connecticut, Sch Nursing, Storrs, CT USA.
[Cong, Xiaomei; Graf, Joerg] Univ Connecticut, Inst Syst Genom, Farmington, CT USA.
[Janton, Susan; Graf, Joerg] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT USA.
[Henderson, Wendy A.] NINR, Digest Disorders Unit, Biobehav Branch, NIH, Bethesda, MD 20892 USA.
[Matson, Adam; McGrath, Jacqueline M.] Connecticut Childrens Med Ctr, Hartford, CT USA.
[Maas, Kendra] Univ Connecticut, Microbial Anal Resources & Serv, Storrs, CT USA.
RP Cong, XM (reprint author), Univ Connecticut, Sch Nursing, Storrs, CT USA.; Cong, XM (reprint author), Univ Connecticut, Inst Syst Genom, Farmington, CT USA.
EM xiaomei.cong@uconn.edu
OI Henderson, Wendy/0000-0003-3924-7118
FU National Institute of Nursing Research of the National Institutes of
Health (NIH-NINR) [K23NR014674]; Affinity Research Collaboratives award
through University of Connecticut Institute for Systems Genomics
FX This publication was supported by the National Institute of Nursing
Research of the National Institutes of Health (NIH-NINR) under award
number K23NR014674 and Affinity Research Collaboratives award through
University of Connecticut Institute for Systems Genomics. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 50
TC 6
Z9 6
U1 8
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 25
PY 2016
VL 11
IS 4
AR e0152751
DI 10.1371/journal.pone.0152751
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK5OX
UT WOS:000374970600005
PM 27111847
ER
PT J
AU Kilic, S
Sagitova, DM
Wolfish, S
Bely, B
Courtot, M
Ciufo, S
Tatusova, T
O'Donovan, C
Chibucos, MC
Martin, MJ
Erill, I
AF Kilic, Sefa
Sagitova, Dinara M.
Wolfish, Shoshannah
Bely, Benoit
Courtot, Melanie
Ciufo, Stacy
Tatusova, Tatiana
O'Donovan, Claire
Chibucos, Marcus C.
Martin, Maria J.
Erill, Ivan
TI From data repositories to submission portals: rethinking the role of
domain-specific databases in CollecTF
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID SEQUENCES; ONTOLOGY; BIOLOGY; TOOLS; DNA
AB Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.
C1 [Kilic, Sefa; Sagitova, Dinara M.; Erill, Ivan] Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
[Wolfish, Shoshannah; Chibucos, Marcus C.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Bely, Benoit; Courtot, Melanie; O'Donovan, Claire; Martin, Maria J.] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
[Ciufo, Stacy; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A, Bethesda, MD 20894 USA.
[Chibucos, Marcus C.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Erill, I (reprint author), Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM erill@umbc.edu
OI Courtot, Melanie/0000-0002-9551-6370; O'Donovan,
Claire/0000-0001-8051-7429; Chibucos, Marcus/0000-0001-9586-0780
FU US National Science Foundation Division of Molecular and Cellular
Biosciences [MCB-1158056]; US National Institutes of Health/National
Human Genome Research Institute [U41HG007822, U41HG002273]; US National
Science Foundation Division of Biological Infrastructure Award
[DBI-1458400]; European Molecular Biology Laboratory core funds. Funding
for open access charge: US National Sciences Foundation [MCB-1158056]
FX This work was funded by the US National Science Foundation Division of
Molecular and Cellular Biosciences award MCB-1158056 (University of
Maryland Baltimore County), the US National Institutes of
Health/National Human Genome Research Institute grants U41HG007822 and
U41HG002273 (European Bioinformatics Institute - European Molecular
Biology Laboratory), the US National Science Foundation Division of
Biological Infrastructure Award DBI-1458400 (University of Maryland at
Baltimore) and by the European Molecular Biology Laboratory core funds.
Funding for open access charge: US National Sciences Foundation
[MCB-1158056].
NR 30
TC 0
Z9 0
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD APR 25
PY 2016
AR baw055
DI 10.1093/database/baw055
PG 10
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DK1CS
UT WOS:000374650700002
ER
PT J
AU Ghitza, UE
AF Ghitza, Udi E.
TI Commentary: a Gene-Based association method for mapping traits Using
reference transcriptome Data
SO FRONTIERS IN PSYCHIATRY
LA English
DT Editorial Material
DE genetics; gene expression; bioinformatics; informatics; precision
medicine; addiction; drug abuse; substance-use disorders
ID ADDICTION; BRAIN
C1 [Ghitza, Udi E.] NIDA, US Dept HHS, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA.
RP Ghitza, UE (reprint author), NIDA, US Dept HHS, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA.
EM ghitzau@nida.nih.gov
NR 10
TC 0
Z9 0
U1 3
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-0640
J9 FRONT PSYCHIATRY
JI Front. Psychiatry
PD APR 25
PY 2016
VL 7
AR 73
DI 10.3389/fpsyt.2016.00073
PG 3
WC Psychiatry
SC Psychiatry
GA DK0VT
UT WOS:000374631000003
PM 27199780
ER
PT J
AU Zhao, ZL
Zhang, L
Huang, CF
Ma, SR
Bu, LL
Liu, JF
Yu, GT
Liu, B
Gutkind, JS
Kulkarni, AB
Zhang, WF
Sun, ZJ
AF Zhao, Zhi-Li
Zhang, Lu
Huang, Cong-Fa
Ma, Si-Rui
Bu, Lin-Lin
Liu, Jian-Feng
Yu, Guang-Tao
Liu, Bing
Gutkind, J. Silvio
Kulkarni, Ashok B.
Zhang, Wen-Feng
Sun, Zhi-Jun
TI NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic
agents by targeting head neck cancer stem cell
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GAMMA-SECRETASE INHIBITOR; ADVANCED
SOLID TUMORS; SIGNALING PATHWAY; GENOMIC CHARACTERIZATION;
PANCREATIC-CANCER; IN-VIVO; CARCINOMA; MUTATIONS; GROWTH
AB Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal ability in vitro and in vivo. Flow cytometry analysis showed that NOTCH1 inhibition reduces CSCs frequency either alone or in combination with chemotherapeutic agents, namely, cisplatin, docetaxel, and 5-fluorouracil. The combined strategy of NOTCH1 blockade and chemotherapy synergistically attenuated chemotherapy-enriched CSC population, promising a potential therapeutic exploitation in future clinical trial.
C1 [Zhao, Zhi-Li; Zhang, Lu; Huang, Cong-Fa; Ma, Si-Rui; Bu, Lin-Lin; Liu, Jian-Feng; Yu, Guang-Tao; Sun, Zhi-Jun] Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China.
[Zhao, Zhi-Li; Zhang, Lu; Huang, Cong-Fa; Ma, Si-Rui; Bu, Lin-Lin; Liu, Jian-Feng; Yu, Guang-Tao; Sun, Zhi-Jun] Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China.
[Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan 430072, Peoples R China.
[Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Kulkarni, Ashok B.; Sun, Zhi-Jun] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Sun, ZJ (reprint author), Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China.; Sun, ZJ (reprint author), Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China.; Sun, ZJ (reprint author), Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan 430072, Peoples R China.; Sun, ZJ (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
EM zhijundejia@163.com
FU National Natural Science Foundation of China [81272963, 81472528,
81272964, 81472529, 81402241]; Division of Intramural Research, NIDCR,
NIH, USA; program for new century excellent talents in university,
Ministry of Education of China [NCET-13-0439]
FX This work was supported by National Natural Science Foundation of China
81272963, 81472528 (Z.J.S.), 81272964, 81472529 (W.F.Z.), 81402241
(C.F.H.), and the Division of Intramural Research, NIDCR, NIH, USA
(A.B.K, J.S.G.). Z.J.S. was supported by program for new century
excellent talents in university (NCET-13-0439), Ministry of Education of
China.
NR 51
TC 6
Z9 6
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 25
PY 2016
VL 6
AR 24704
DI 10.1038/srep24704
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK0YX
UT WOS:000374640100001
PM 27108536
ER
PT J
AU Mercredi, PY
Bucca, N
Loeliger, B
Gaines, CR
Mehta, M
Bhargava, P
Tedbury, PR
Charlier, L
Floquet, N
Muriaux, D
Favard, C
Sanders, CR
Freed, EO
Marchant, J
Summers, MF
AF Mercredi, Peter Y.
Bucca, Nadine
Loeliger, Burk
Gaines, Christy R.
Mehta, Mansi
Bhargava, Pallavi
Tedbury, Philip R.
Charlier, Landry
Floquet, Nicolas
Muriaux, Delphine
Favard, Cyril
Sanders, Charles R.
Freed, Eric O.
Marchant, Jan
Summers, Michael F.
TI Structural and Molecular Determinants of Membrane Binding by the HIV-1
Matrix Protein
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE HIV-1 matrix protein; PIP2; bicelles; polysomes; membrane targeting
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRION-ASSOCIATED CHOLESTEROL;
COARSE-GRAINED MODEL; B METHYL-ESTER; PLASMA-MEMBRANE; LIPID RAFTS;
TYPE-1 GAG; BACKBONE DYNAMICS; NMR-SPECTROSCOPY; MYRISTATE EXPOSURE
AB Assembly of HIV-1 particles is initiated by the trafficking of viral Gag polyproteins from the cytoplasm to the plasma membrane, where they co-localize and bud to form immature particles. Membrane targeting is mediated by the N-terminally myristoylated matrix (MA) domain of Gag and is dependent on the plasma membrane marker phosphatidylinositol-4,5-bisphosphate [PI(4,5)P-2]. Recent studies revealed that PI(4,5)P-2 molecules containing truncated acyl chains [tr-PI(4,5)P-2] are capable of binding MA in an "extended lipid" conformation and promoting myristoyl exposure. Here we report that tr-PI(4,5)P-2 molecules also readily bind to non-membrane proteins, including HIV-1 capsid, which prompted us to re-examine MA-PI(4,5)P-2 interactions using native lipids and membrane mimetic liposomes and bicelles. Liposome binding trends observed using a recently developed NMR approach paralleled results of flotation assays, although the affinities measured under the equilibrium conditions of NMR experiments were significantly higher. Native PI(4,5)P-2 enhanced MA binding to liposomes designed to mimic non-raft-like regions of the membrane, suggesting the possibility that binding of the protein to disordered domains may precede Gag association with, or nucleation of, rafts. Studies with bicelles revealed a subset of surface and myr-associated MA residues that are sensitive to native PI(4,5)P-2, but cleft residues that interact with the 2'-acyl chains of tr-PI(4,5)P-2 molecules in aqueous solution were insensitive to native PI(4,5)P-2 in bicelles. Our findings call to question extended-lipid MA:membrane binding models, and instead support a model put forward from coarse-grained simulations indicating that binding is mediated predominantly by dynamic, electrostatic interactions between conserved basic residues of MA and multiple PI(4,5)P-2 and phosphatidylserine molecules. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Mercredi, Peter Y.; Bucca, Nadine; Loeliger, Burk; Gaines, Christy R.; Mehta, Mansi; Bhargava, Pallavi; Marchant, Jan; Summers, Michael F.] Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Tedbury, Philip R.; Freed, Eric O.] NCI, HIV Dynam & Replicat Program, Virus Cell Interact Sect, Frederick, MD 21702 USA.
[Charlier, Landry; Floquet, Nicolas] Univ Montpellier, Fac Pharm, CNRS UMR5247, Inst Biomol Max Mousseron, F-34059 Montpellier 05, France.
[Muriaux, Delphine; Favard, Cyril] Univ Montpellier, CNRS, UMR 5236, Ctr Etud Agents Pathogenes & Biotechnol Sante, F-34059 Montpellier 5, France.
[Sanders, Charles R.] Vanderbilt Univ, Sch Med, Struct Biol Ctr, Dept Biochem, Nashville, TN 37240 USA.
[Sanders, Charles R.] Vanderbilt Univ, Sch Med, Inst Chem Biol, Nashville, TN 37240 USA.
RP Marchant, J; Summers, MF (reprint author), Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Dept Chem & Biochem, Baltimore, MD 21250 USA.; Freed, EO (reprint author), NCI, HIV Dynam & Replicat Program, Virus Cell Interact Sect, Frederick, MD 21702 USA.
EM efreed@mail.nih.gov; janm@umbc.edu; summers@hhmi.umbc.edu
RI Favard, Cyril/P-6392-2016;
OI Favard, Cyril/0000-0002-8304-2980; Tedbury, Philip/0000-0001-8151-4967
FU NIH [AI30917, GM103297, GM106672]; NIGMS [R25-GM55036]
FX Support from NIH grants AI30917 and GM103297 (to M.F.S.) and GM106672
(to C.S.) is gratefully acknowledged. P.Y.M. was supported by an NIGMS
Initiative for Minority Student Development grant, R25-GM55036.
NR 109
TC 8
Z9 8
U1 8
U2 20
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD APR 24
PY 2016
VL 428
IS 8
BP 1637
EP 1655
DI 10.1016/j.jmb.2016.03.005
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL0PU
UT WOS:000375335800012
PM 26992353
ER
PT J
AU Rajpert-De Meyts, E
McGlynn, KA
Okamoto, K
Jewett, MAS
Bokemeyer, C
AF Rajpert-De Meyts, Ewa
McGlynn, Katherine A.
Okamoto, Keisei
Jewett, Michael A. S.
Bokemeyer, Carsten
TI Testicular germ cell tumours
SO LANCET
LA English
DT Review
ID CARCINOMA-IN-SITU; HIGH-DOSE CHEMOTHERAPY; CANCER-STUDY-GROUP;
LYMPH-NODE DISSECTION; RANDOMIZED PHASE-III; SUBCENTIMETER RESIDUAL
MASS; MEDICAL-RESEARCH-COUNCIL; LONG-TERM SURVIVORS; OF-THE-LITERATURE;
FOLLOW-UP
AB Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors.
C1 [Rajpert-De Meyts, Ewa] Rigshosp, Copenhagen Univ Hosp, Dept Growth & Reprod, DK-2100 Copenhagen, Denmark.
[Rajpert-De Meyts, Ewa] Int Ctr Res & Res Training Endocrine Disrupting E, Copenhagen, Denmark.
[McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Okamoto, Keisei] Shiga Univ Med Sci, Dept Urol, Shiga 5202192, Japan.
[Jewett, Michael A. S.] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Surg Urol, Toronto, ON, Canada.
[Jewett, Michael A. S.] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Surg Oncol, Toronto, ON, Canada.
[Jewett, Michael A. S.] Univ Toronto, Toronto, ON, Canada.
[Bokemeyer, Carsten] Univ Hosp Hamburg Eppendorf, Dept Med, Dept Oncol Haematol Bone Marrow Transplantat, Sect Pneumol, Hamburg, Germany.
RP Okamoto, K (reprint author), Shiga Univ Med Sci, Dept Urol, Shiga 5202192, Japan.
EM keisei@belle.shiga-med.ac.jp
FU Danish Cancer Society; National Cancer Institute
FX We thank Kahori Minami for assistance in the collection and collation of
reference material. Our work was supported by grants from the Danish
Cancer Society (to ERDM), and the National Cancer Institute's Intramural
Research Program (to KAM), but the supporting institutes had no role in
this Seminar.
NR 157
TC 8
Z9 8
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD APR 23
PY 2016
VL 387
IS 10029
BP 1762
EP 1774
DI 10.1016/S0140-6736(15)00991-5
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ9OD
UT WOS:000374541900029
PM 26651223
ER
PT J
AU Urzua, U
Ampuero, S
Roby, KF
Owens, GA
Munroe, DJ
AF Urzua, Ulises
Ampuero, Sandra
Roby, Katherine F.
Owens, Garrison A.
Munroe, David J.
TI Dysregulation of mitotic machinery genes precedes genome instability
during spontaneous pre-malignant transformation of mouse ovarian surface
epithelial cells
SO BMC GENOMICS
LA English
DT Article
DE Ovarian cancer model; Preneoplasia; Mouse ovarian surface epithelium;
Transcriptome; Genome; Aneuploidy; Cytokinesis; DNA microarrays
ID LONG NONCODING RNA; TUMOR-SUPPRESSOR GENES; FUNCTIONAL-CHARACTERISTICS;
RACGAP1 EXPRESSION; COLORECTAL-CANCER; NUCLEAR RETENTION; INCLUSION
CYSTS; MESSENGER-RNA; MURINE MODEL; RISK-FACTORS
AB Background: Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE). Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE) cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model.
Results: At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05) comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1), Birc5 (Survivin), Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci.
Conclusion: Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes suggests altered control of nuclear RNA maturation, features recently linked to impaired DNA damage response leading to genome instability. These results, combined with cytogenetic analysis by other authors in this model, suggest that transcriptional profile at passage 14 might induce cytokinesis failure by which tetraploid cells approach a near-tetraploid stage containing primary chromosome aberrations that initiate the tumorigenic drive.
C1 [Urzua, Ulises] Univ Chile, Fac Med, Programa Biol Celular & Mol, Lab Genom Aplicada,ICBM, Santiago 1027, Chile.
[Ampuero, Sandra] Univ Chile, Fac Med, Programa Virol, ICBM, Santiago 1027, Chile.
[Roby, Katherine F.] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA.
[Owens, Garrison A.; Munroe, David J.] NCI SAIC Frederick, Lab Mol Technol, Frederick, MD USA.
[Munroe, David J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD USA.
[Owens, Garrison A.] ThermoFisher Sci, Life Sci Solut Grp, 5792 Van Allen Way, Carlsbad, CA 92008 USA.
RP Urzua, U (reprint author), Univ Chile, Fac Med, Programa Biol Celular & Mol, Lab Genom Aplicada,ICBM, Santiago 1027, Chile.
EM uurzua@med.uchile.cl
FU Fondecyt [1130292]; Ministry of Education, Chile [N01-CO-12400];
NCI-NIH, USA
FX This work was funded by grant Fondecyt 1130292, Ministry of Education,
Chile (UU) and contract N01-CO-12400, NCI-NIH, USA (DJM). Funding for
publication was from grant Fondecyt 1130292.
NR 67
TC 0
Z9 0
U1 4
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD APR 22
PY 2016
VL 17
SU 8
AR 728
DI 10.1186/s12864-016-3068-5
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA EJ0UN
UT WOS:000392926100004
PM 27801298
ER
PT J
AU Waheed, AA
MacDonald, S
Khan, M
Mounts, M
Swiderski, M
Xu, Y
Ye, YH
Freed, EO
AF Waheed, Abdul A.
MacDonald, Scott
Khan, Maisha
Mounts, Megan
Swiderski, Maya
Xu, Yue
Ye, Yihong
Freed, Eric O.
TI The Vpu-interacting Protein SGTA Regulates Expression of a
Non-glycosylated Tetherin Species
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RICH TETRATRICOPEPTIDE REPEAT; CYTOSOLIC
QUALITY-CONTROL; TPR-CONTAINING PROTEIN; ENDOPLASMIC-RETICULUM;
DOWN-REGULATION; MANNOSIDASE-I; HIV-1 VPU; FUNCTIONAL INTERACTION;
MISLOCALIZED PROTEINS
AB The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu-and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.
C1 [Waheed, Abdul A.; MacDonald, Scott; Khan, Maisha; Mounts, Megan; Swiderski, Maya; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Xu, Yue; Ye, Yihong] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Waheed, AA (reprint author), NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM waheedab@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH; Intramural
AIDS Targeted Antiviral Program
FX We thank Myriad Genetics (Salt Lake City, UT) for carrying out yeast
two-hybrid screening. We thank members of the Freed laboratory for
helpful discussion and critical review of the manuscript. We thank K.
Strebel, and P. Bieniasz for their generous gifts of plasmids. The HIV-1
Ig, anti-Vpu and anti-human tetherin antisera were obtained from the NIH
AIDS Research and Reference Reagent Program. Research in the Freed
laboratory is supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH, and by the
Intramural AIDS Targeted Antiviral Program.
NR 64
TC 0
Z9 0
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 22
PY 2016
VL 6
AR 24934
DI 10.1038/srep24934
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK2NQ
UT WOS:000374752100001
PM 27103333
ER
PT J
AU Tryndyak, VP
Han, T
Fuscoe, JC
Ross, SA
Beland, FA
Pogribny, IP
AF Tryndyak, Volodymyr P.
Han, Tao
Fuscoe, James C.
Ross, Sharon A.
Beland, Frederick A.
Pogribny, Igor P.
TI Status of hepatic DNA methylome predetermines and modulates the severity
of non-alcoholic fatty liver injury in mice
SO BMC GENOMICS
LA English
DT Article
DE DNA methylation; Non-alcoholic fatty liver injury; Susceptibility;
Mouse; Inter-strain differences
ID FOLATE-DEFICIENT DIET; NAFLD PROGRESSION; WIDE ASSOCIATION; DISEASE;
METHYLATION; STEATOHEPATITIS; STEATOSIS; PNPLA3; GENE; VARIANTS
AB Background: Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and Western countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD; nonetheless, the effect of inter-individual differences in the normal liver epigenome with regard to the susceptibility to NAFLD has not been determined.
Results: In the present study, we investigated the association between the DNA methylation status in the livers of A/J and WSB/EiJ mice and the severity of NAFLD-associated liver injury. We demonstrate that A/J and WSB/EiJ mice, which are characterized by significant differences in the severity of liver injury induced by a choline- and folate-deficient (CFD) diet exhibit substantial differences in cytosine DNA methylation in their normal livers. Furthermore, feeding A/J and WSB/EiJ mice a CFD diet for 12 weeks resulted in different trends and changes in hepatic cytosine DNA methylation.
Conclusion: Our findings indicate a primary role of hepatic DNA methylation in the pathogenesis of NAFLD and suggest that individual variations in DNA methylation across the genome may be a factor determining and influencing the vulnerability to NAFLD.
C1 [Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
[Han, Tao; Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
[Ross, Sharon A.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
RP Pogribny, IP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
FU FDA-NCTR Intramural Research Program (Jefferson, AR, USA)
FX This study was funded by the FDA-NCTR Intramural Research Program
(Jefferson, AR, USA).
NR 38
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD APR 22
PY 2016
VL 17
AR 298
DI 10.1186/s12864-016-2617-2
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DK5FO
UT WOS:000374945500001
PM 27103143
ER
PT J
AU Hong, E
Usiskin, IM
Bergamaschi, C
Hanlon, DJ
Edelson, RL
Justesen, S
Pavlakis, GN
Flavell, RA
Fahmy, TM
AF Hong, Enping
Usiskin, Ilana M.
Bergamaschi, Cristina
Hanlon, Douglas J.
Edelson, Richard L.
Justesen, Sune
Pavlakis, George N.
Flavell, Richard A.
Fahmy, Tarek M.
TI Configuration-dependent Presentation of Multivalent IL-15: IL-15R alpha
Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN DENDRITIC CELLS; TUMOR-INFILTRATING LYMPHOCYTES; IN-VIVO;
CROSS-PRESENTATION; ADOPTIVE IMMUNOTHERAPY; TRANS-PRESENTATION;
RECEPTOR-ALPHA; BIODEGRADABLE NANOPARTICLES; SOLUBLE IL-15R-ALPHA; HUMAN
INTERLEUKIN-15
AB Here we report a "configuration-dependent" mechanism of action for IL-15:IL-15R alpha (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15R alpha molecules are presented to target cells significantly affects its function as a vaccine adjuvant. Although the cellular mechanism of IL-15 trans-presentation via IL-15R alpha and its importance for IL-15 function have been described, the full effect of the IL-15:IL-15R alpha configuration on responding cells is not yet known. We found that trans-presenting IL-15:IL-15R alpha in a multivalent fashion on the surface of antigen-encapsulating nanoparticles enhanced the ability of nanoparticle-treated dendritic cells (DCs) to stimulate antigen-specific CD8(+) T cell responses. Localization of multivalent IL-15:IL-15R alpha and encapsulated antigen to the same DC led to maximal T cell responses. Strikingly, DCs incubated with IL-15:IL-15R alpha coated nanoparticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for nanoparticle-mediated transfer of IL-15 to the DC surface. Using artificial antigen-presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial antigen-presenting cells presenting IL-15:IL-15R alpha increased the sensitivity and magnitude of the T cell response, whereas IL-2 enhanced the T cell response only when delivered in a paracrine fashion. Therefore, the mode of cytokine presentation (configuration) is important for optimal immune responses. We tested the effect of configuration dependence in an aggressive model of murine melanoma and demonstrated significantly delayed tumor progression induced by IL-15:IL-15R alpha-coated nanoparticles in comparison with monovalent IL-15:IL-15R alpha. The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs may explain the enhanced potency of IL-15:IL-15R alpha-coated nanoparticles for antigen delivery.
C1 [Hong, Enping; Usiskin, Ilana M.; Fahmy, Tarek M.] Yale Univ, Dept Biomed Engn, 55 Prospect St, New Haven, CT 06511 USA.
[Flavell, Richard A.; Fahmy, Tarek M.] Yale Univ, Sch Med, Dept Immunobiol, 55 Prospect St, New Haven, CT 06511 USA.
[Hanlon, Douglas J.; Edelson, Richard L.] Yale Univ, Sch Med, Dept Dermatol, 55 Prospect St, New Haven, CT 06511 USA.
[Bergamaschi, Cristina; Pavlakis, George N.] NCI, Vaccine Branch, NIH, Frederick, MD 21702 USA.
[Justesen, Sune] Univ Copenhagen, Dept Sci, DK-1017 Copenhagen, Denmark.
RP Fahmy, TM (reprint author), Yale Univ, Dept Biomed Engn, Dept Chem, 55 Prospect St, New Haven, CT 06511 USA.; Fahmy, TM (reprint author), Yale Univ, Dept Environm Engn, Dept Immunobiol, 55 Prospect St, New Haven, CT 06511 USA.; Fahmy, TM (reprint author), Yale Univ, Dept Obstet & Gynecol, 55 Prospect St, New Haven, CT 06511 USA.
EM tarek.fahmy@yale.edu
OI Flavell, Richard/0000-0003-4461-0778
NR 107
TC 1
Z9 1
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 22
PY 2016
VL 291
IS 17
BP 8931
EP 8950
DI 10.1074/jbc.M115.695304
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK3WV
UT WOS:000374849000007
PM 26719339
ER
PT J
AU Montecinos-Franjola, F
Schuck, P
Sackett, DL
AF Montecinos-Franjola, Felipe
Schuck, Peter
Sackett, Dan L.
TI Tubulin Dimer Reversible Dissociation AFFINITY, KINETICS, AND
DEMONSTRATION OF A STABLE MONOMER
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ALPHA-BETA-TUBULIN; SEDIMENTATION-VELOCITY; PROTEIN INTERACTIONS;
FLUORESCENCE ANISOTROPY; MICROTUBULE DYNAMICS; COLCHICINE BINDING;
POLYMERIZATION; ASSOCIATION; SUBUNITS; COMPLEX
AB Tubulins are evolutionarily conserved proteins that reversibly polymerize and direct intracellular traffic. Of the tubulin family only alpha beta-tubulin forms stable dimers. We investigated the monomer-dimer equilibrium of rat brain alpha beta-tubulin using analytical ultracentrifugation and fluorescence anisotropy, observing tubulin in virtually fully monomeric and dimeric states. Monomeric tubulin was stable for a few hours and exchanged into preformed dimers, demonstrating reversibility of dimer dissociation. Global analysis combining sedimentation velocity and fluorescence anisotropy yielded K-d = 84 (54-123) nM. Dimer dissociation kinetics were measured by analyzing the shape of the sedimentation boundary and by the relaxation of fluorescence anisotropy following rapid dilution of labeled tubulin, yielding k(off) in the range 10(-3)-10(-2) s(-1). Thus, tubulin dimers reversibly dissociate with moderately fast kinetics. Monomer-monomer association is much less sensitive than dimer-dimer association to solution changes (GTP/GDP, urea, and trimethylamine oxide).
C1 [Montecinos-Franjola, Felipe; Sackett, Dan L.] Natl Inst Biomed Imaging & Bioengn NHBLI, Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Schuck, Peter] Natl Inst Biomed Imaging & Bioengn NHBLI, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Montecinos-Franjola, F (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bldg 9,Rm 1E-122,9000 Rockville Pike, Bethesda, MD 20892 USA.; Sackett, DL (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bldg 9,Rm 1E-129,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM felipe.montecinos@nih.gov; sackettd@mail.nih.gov
OI Montecinos-Franjola, Felipe/0000-0002-1823-103X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Biomedical Imaging and Bioengineering
(NHBLI), National Institutes of Health, Bethesda, MD
FX This work was supported by funds of the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, and the National Institute of Biomedical Imaging and
Bioengineering (NHBLI), National Institutes of Health, Bethesda, MD. The
authors declare that they have no conflicts of interest with the
contents of this article. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 61
TC 1
Z9 1
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 22
PY 2016
VL 291
IS 17
BP 9281
EP 9294
DI 10.1074/jbc.M115.699728
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK3WV
UT WOS:000374849000037
PM 26934918
ER
PT J
AU Sirohi, D
Chen, ZG
Sun, L
Klose, T
Pierson, TC
Rossmann, MG
Kuhn, RJ
AF Sirohi, Devika
Chen, Zhenguo
Sun, Lei
Klose, Thomas
Pierson, Theodore C.
Rossmann, Michael G.
Kuhn, Richard J.
TI The 3.8 angstrom resolution cryo-EM structure of Zika virus
SO SCIENCE
LA English
DT Article
ID WEST-NILE-VIRUS; DENGUE VIRUS; TRANSMISSION; MATURATION; MICRONESIA;
INFECTION; COMPLEX; BRAZIL
AB The recent rapid spread of Zika virus and its unexpected linkage to birth defects and an autoimmune neurological syndrome have generated worldwide concern. Zika virus is a flavivirus like the dengue, yellow fever, and West Nile viruses. We present the 3.8 angstrom resolution structure of mature Zika virus, determined by cryo-electron microscopy (cryo-EM). The structure of Zika virus is similar to other known flavivirus structures, except for the similar to 10 amino acids that surround the Asn(154) glycosylation site in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, which is recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses, which suggests that differences in this region may influence virus transmission and disease.
C1 [Sirohi, Devika; Chen, Zhenguo; Sun, Lei; Klose, Thomas; Rossmann, Michael G.; Kuhn, Richard J.] Purdue Univ, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.
[Sirohi, Devika; Chen, Zhenguo; Sun, Lei; Klose, Thomas; Rossmann, Michael G.; Kuhn, Richard J.] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
[Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Rossmann, MG; Kuhn, RJ (reprint author), Purdue Univ, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA.; Rossmann, MG; Kuhn, RJ (reprint author), Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
EM mr@purdue.edu; kuhnr@purdue.edu
FU National Institute of Allergy and Infectious Diseases of the NIH
[R01AI073755, R01AI076331]; National Institute of Allergy and Infectious
Diseases
FX We thank X. de Lamballerie (Emergence des Pathologies Virales,
Aix-Marseille Universite, Marseille, France) and the European Virus
Archive Goes Global (EVAg) for consenting to the use of the H/PF/2013
ZIKV strain for this study under a material transfer agreement with
EVAg's partner, Aix-Marseille Universite, and we thank M. S. Diamond
(Washington University, St. Louis, MO, USA) for sending the virus. We
acknowledge E. Frye for help with sequence alignments. We also
acknowledge the use of the Purdue cryo-EM facility. We are grateful to
W. Jiang for his jspr program, which was used to perform the anisotropic
magnification corrections, and Y. Liu for providing help in submitting
the Protein Data Bank (PDB) coordinates. The work presented in this
report was funded by the National Institute of Allergy and Infectious
Diseases of the NIH through grants R01AI073755 and R01AI076331 to M.G.R.
and R.J.K. T.C.P was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases. Supporting information for
this research is provided in the supplementary materials. The atomic
coordinates and cryo-EM density maps for the mature ZIKV are available
at the PDB and Electron Microscopy Data Bank under accession codes 5IRE
and EMD-8116, respectively.
NR 36
TC 63
Z9 68
U1 29
U2 54
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD APR 22
PY 2016
VL 352
IS 6284
BP 467
EP 470
DI 10.1126/science.aaf5316
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ8RH
UT WOS:000374479700049
PM 27033547
ER
PT J
AU Davey, JR
Watt, KI
Parker, BL
Chaudhuri, R
Ryall, JG
Cunningham, L
Qian, H
Sartorelli, V
Sandri, M
Chamberlain, J
James, DE
Gregorevic, P
AF Davey, Jonathan R.
Watt, Kevin I.
Parker, Benjamin L.
Chaudhuri, Rima
Ryall, James G.
Cunningham, Louise
Qian, Hongwei
Sartorelli, Vittorio
Sandri, Marco
Chamberlain, Jeffrey
James, David E.
Gregorevic, Paul
TI Integrated expression analysis of muscle hypertrophy identifies Asb2 as
a negative regulator of muscle mass
SO JCI INSIGHT
LA English
DT Article
ID LIGASE SPECIFICITY SUBUNIT; PROTEASOMAL DEGRADATION; CANCER CACHEXIA;
ACTIVIN-A; MYOSTATIN; MICE; FOLLISTATIN; INHIBITION; SARCOPENIA; GROWTH
AB The transforming growth factor-beta (TGF-beta) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-beta network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-beta network-responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles.
C1 [Davey, Jonathan R.; Watt, Kevin I.; Cunningham, Louise; Qian, Hongwei; Gregorevic, Paul] Baker IDI Heart & Diabet Inst, POB 6492, Melbourne, Vic 3004, Australia.
[Parker, Benjamin L.; Chaudhuri, Rima; James, David E.] Univ Sydney, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW, Australia.
[Ryall, James G.; Sartorelli, Vittorio] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Ryall, James G.; Gregorevic, Paul] Univ Melbourne, Dept Physiol, Melbourne, Vic, Australia.
[Sandri, Marco] Univ Padua, Venetian Inst Mol Med, Padua, Italy.
[Chamberlain, Jeffrey; Gregorevic, Paul] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[James, David E.] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia.
[Gregorevic, Paul] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
RP Gregorevic, P (reprint author), Baker IDI Heart & Diabet Inst, POB 6492, Melbourne, Vic 3004, Australia.
EM Paul.Gregorevic@BakerIDI.edu.au
NR 54
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD APR 21
PY 2016
VL 1
IS 5
AR e85477
DI 10.1172/jci.insight.85477
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1IV
UT WOS:000387104600002
ER
PT J
AU Kanakry, CG
Coffey, DG
Towlerton, AMH
Vulic, A
Storer, BE
Chou, J
Yeung, CCS
Gocke, CD
Robins, HS
O'Donnell, PV
Luznik, L
Warren, EH
AF Kanakry, Christopher G.
Coffey, David G.
Towlerton, Andrea M. H.
Vulic, Ante
Storer, Barry E.
Chou, Jeffrey
Yeung, Cecilia C. S.
Gocke, Christopher D.
Robins, Harlan S.
O'Donnell, Paul V.
Luznik, Leo
Warren, Edus H.
TI Origin and evolution of the T cell repertoire after posttransplantation
cyclophosphamide
SO JCI INSIGHT
LA English
DT Article
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MINOR
HISTOCOMPATIBILITY ANTIGENS; EPSTEIN-BARR-VIRUS; HEMATOLOGIC
MALIGNANCIES; CYTOMEGALOVIRUS-SEROPOSITIVITY; PERIPHERAL-BLOOD; IMMUNE
RECOVERY; SINGLE-AGENT; CHRONIC GVHD
AB Posttransplantation cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD), but its immunologic impact is poorly understood. We assessed lymphocyte reconstitution via flow cytometry (n = 74) and antigen receptor sequencing (n = 35) in recipients of myeloablative, HLA-matched allogeneic BM transplantation using PTCy. Recovering T cells were primarily phenotypically effector memory with lower T cell receptor beta (TRB) repertoire diversity than input donor repertoires. Recovering B cells were predominantly naive with immunoglobulin heavy chain locus (IGH) repertoire diversity similar to donors. Numerical T cell reconstitution and TRB diversity were strongly associated with recipient cytomegalovirus seropositivity. Global similarity between input donor and recipient posttransplant repertoires was uniformly low at 1-2 months after transplant but increased over the balance of the first posttransplant year. Blood TRB repertoires at >= 3 months after transplant were often dominated by clones present in the donor blood/marrow memory CD8(+) compartment. Limited overlap was observed between the TRB repertoires of T cells infiltrating the skin or gastrointestinal tract versus the blood. Although public TRB sequences associated with herpesvirus-or alloantigen-specific CD8(+) T cells were detected in some patients, posttransplant TRB and IGH repertoires were unique to each individual. These data define the immune dynamics occurring after PTCy and establish a benchmark against which immune recovery after other transplantation approaches can be compared.
C1 [Kanakry, Christopher G.; Vulic, Ante; Gocke, Christopher D.; Luznik, Leo] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Coffey, David G.; Towlerton, Andrea M. H.; Storer, Barry E.; Chou, Jeffrey; Yeung, Cecilia C. S.; O'Donnell, Paul V.; Warren, Edus H.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Coffey, David G.; Chou, Jeffrey; O'Donnell, Paul V.; Warren, Edus H.] Univ Washington, Dept Med, Seattle, WA USA.
[Yeung, Cecilia C. S.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Robins, Harlan S.] FHCRC, Publ Hlth Sci Div, Seattle, WA USA.
[Kanakry, Christopher G.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Warren, EH (reprint author), 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA.; Luznik, L (reprint author), 1650 Orleans St, Baltimore, MD 21287 USA.
EM luznile@jhmi.edu; ehwarren@u.washington.edu
NR 57
TC 1
Z9 1
U1 1
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD APR 21
PY 2016
VL 1
IS 5
AR e86252
DI 10.1172/jci.insight.86252
PG 20
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1IV
UT WOS:000387104600008
ER
PT J
AU Her, NG
Toth, JI
Ma, CT
Wei, Y
Motamedchaboki, K
Sergienko, E
Petroski, MD
AF Her, Nam-Gu
Toth, Julia I.
Ma, Chen-Ting
Wei, Yang
Motamedchaboki, Khatereh
Sergienko, Eduard
Petroski, Matthew D.
TI p97 Composition Changes Causedby Allosteric Inhibition Are Suppressed by
an On-Target Mechanism that Increases the Enzyme's ATPase Activity
SO CELL CHEMICAL BIOLOGY
LA English
DT Article
ID UBIQUITIN-PROTEASOME SYSTEM; AAA-ATPASE; MEMBRANE-FUSION; PROTEIN;
VCP/P97; ER; CDC48/P97; DOMAIN; COMPLEX; P97/VCP
AB The AAA ATPase p97/VCP regulates protein homeostasis using a diverse repertoire of cofactors to fulfill its biological functions. Here we use the allosteric p97 inhibitor NMS-873 to analyzeits effects on enzyme composition and the ability of cells to adapt to its cytotoxicity. We found that p97 inhibition changes steady state cofactor-p97 composition, leading to the enrichment of a subset of its cofactors and polyubiquitin bound to p97. We isolated cells specifically insensitive to NMS-873 and identified a new mutation (A530T) in p97. A530T is sufficient to overcome the cytotoxicity of NMS-873 and alleviates p97 composition changes caused by the molecule but not other p97 inhibitors. This mutation does not affect NMS-873 binding but increases p97 catalytic efficiency through altered ATP and ADP binding. Collectively, these findings identify cofactor-p97 interactions sensitive to p97 inhibition and reveal a new on-target mechanism to suppress the cytotoxicity of NMS-873.
C1 [Her, Nam-Gu; Toth, Julia I.; Wei, Yang; Motamedchaboki, Khatereh; Petroski, Matthew D.] NCI, Tumor Initiat & Maintenance Program, Designated Canc Ctr, Sanford Burnham Prebys Med Discovery Inst, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
[Ma, Chen-Ting; Sergienko, Eduard] NCI, Conrad Prebys Ctr Chem Genom, Designated Canc Ctr, Sanford Burnham Prebys Med Discovery Inst, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
RP Petroski, MD (reprint author), NCI, Tumor Initiat & Maintenance Program, Designated Canc Ctr, Sanford Burnham Prebys Med Discovery Inst, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM petroski@sbpdiscovery.org
FU National Cancer Institute of the NIH (Cancer Center Support Grant) [R01
CA180150, R21 CA182178, R01 CA185300, P30 CA030199]; American Cancer
Society [RSG-11-224-01-DMC]
FX We thank Brian James for STR genotyping, Tony Pinkerton for sourcing and
evaluating compounds, and Dieter Wolf for helpful discussions. This work
was supported in part by the National Cancer Institute of the NIH (R01
CA180150, R21 CA182178, R01 CA185300, and Cancer Center Support Grant
P30 CA030199), and the American Cancer Society (RSG-11-224-01-DMC).
NR 38
TC 2
Z9 2
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2451-9448
J9 CELL CHEM BIOL
JI Cell Chem. Biol.
PD APR 21
PY 2016
VL 23
IS 4
BP 517
EP 528
DI 10.1016/j.chembiol.2016.03.012
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT5GA
UT WOS:000381508400012
PM 27105284
ER
PT J
AU Kanakry, JA
Hegde, AM
Durand, CM
Massie, AB
Greer, AE
Ambinder, RF
Valsamakis, A
AF Kanakry, Jennifer A.
Hegde, Aparna M.
Durand, Christine M.
Massie, Allan B.
Greer, Amy E.
Ambinder, Richard F.
Valsamakis, Alexandra
TI The clinical significance of EBV DNA in the plasma and peripheral blood
mononuclear cells of patients with or without EBV diseases
SO BLOOD
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; REAL-TIME PCR; POSTTRANSPLANT LYMPHOPROLIFERATIVE
DISORDER; POLYMERASE-CHAIN-REACTION; VIRAL LOAD; NASOPHARYNGEAL
CARCINOMA; T-CELL; HODGKIN LYMPHOMA; NASAL-TYPE; B-CELLS
AB Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV+ disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV+ disease. In patients with active, systemic EBV+ diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV+ disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV+ lymphoma from EBV+ lymphoma in remission and EBV- lymphoma, and also distinguished untreated, EBV+ posttransplantation lymphoproliferative disorder (PTLD) from EBV+ PTLD in remission and EBV- PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV+ diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV+ disease than PBMCs.
C1 [Kanakry, Jennifer A.; Hegde, Aparna M.] Johns Hopkins Univ, Dept Med, Hematol, Baltimore, MD USA.
[Durand, Christine M.] Johns Hopkins Univ, Dept Med, Infect Dis, Baltimore, MD USA.
[Massie, Allan B.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA.
[Greer, Amy E.; Valsamakis, Alexandra] Johns Hopkins Univ, Dept Pathol, Med Microbiol, Baltimore, MD USA.
[Ambinder, Richard F.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Kanakry, Jennifer A.; Ambinder, Richard F.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
RP Kanakry, JA (reprint author), NIH, 10 Ctr Dr,Bldg 10-CRC,Room 4-3132, Bethesda, MD 20892 USA.; Valsamakis, A (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Meyer Bldg,Room B1-193, Baltimore, MD 21287 USA.
EM jennifer.kanakry@nih.gov; avalsam1@jhmi.edu
FU National Institutes of Health [R21 CA188824, P30 CA006973]; Centers for
AIDS Research (National Institute of Allergy and Infectious Diseases,
National Institutes of Health) [P30 AI094189]; National Cancer Institute
FX This study was supported by grants from the National Cancer Institute,
National Institutes of Health (R21 CA188824 and P30 CA006973) (R.F.A.)
and a faculty development award to J.A.K., allocated through the Centers
for AIDS Research (National Institute of Allergy and Infectious
Diseases, National Institutes of Health, P30 AI094189).
NR 43
TC 5
Z9 5
U1 3
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD APR 21
PY 2016
VL 127
IS 16
BP 2007
EP 2017
DI 10.1182/blood-2015-09-672030
PG 11
WC Hematology
SC Hematology
GA DJ8DE
UT WOS:000374441900011
PM 26744460
ER
PT J
AU Chang, JC
Miura, RM
AF Chang, Joshua C.
Miura, Robert M.
TI Regulatory inhibition of biological tissue mineralization by calcium
phosphate through post-nucleation shielding by fetuin-A
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID CONTAINING CALCIPROTEIN PARTICLES; SIMULATED BODY-FLUID; POSNERS
CLUSTER; CALCIFICATION INHIBITION; THEORETICAL-ANALYSIS; SERUM;
PRECIPITATION; CRYSTALLIZATION; COMPLEXES; HYDROXYAPATITE
AB In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids-at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system. Published by AIP Publishing.
C1 [Chang, Joshua C.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Chang, Joshua C.] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA.
[Miura, Robert M.] New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
RP Chang, JC (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.; Chang, JC (reprint author), Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA.; Miura, RM (reprint author), New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
EM joshchang@ucla.edu; miura@njit.edu
FU National Science Foundation [0635561, DMS-1021818]; Army Research Office
[58386MA]; NIH, Clinical Center
FX The authors would like to thank Lydia L. Shook (Yale School of
Medicine), Tom Chou (UCLA Mathematics and Biomathematics), Huaxiong
Huang (York University Mathematics), and Jonathan J. Wylie (City
University of Hong Kong Mathematics) for their comments and feedback
relating to this work. This material is based upon work supported by the
National Science Foundation under Agreement No. 0635561. J.C.C. also
acknowledges support from the National Science Foundation through Grant
No. DMS-1021818, and from the Army Research Office through Grant No.
58386MA. This research was supported in part by the Intramural Research
Program of the NIH, Clinical Center.
NR 46
TC 0
Z9 1
U1 0
U2 5
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD APR 21
PY 2016
VL 144
IS 15
AR 154906
DI 10.1063/1.4946002
PG 13
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DL6YM
UT WOS:000375786000043
PM 27389239
ER
PT J
AU Duy, J
Koehler, JW
Honko, AN
Schoepp, RJ
Wauquier, N
Gonzalez, JP
Pitt, ML
Mucker, EM
Johnson, JC
O'Hearn, A
Bangura, J
Coomber, M
Minogue, TD
AF Duy, Janice
Koehler, Jeffrey W.
Honko, Anna N.
Schoepp, Randal J.
Wauquier, Nadia
Gonzalez, Jean-Paul
Pitt, M. Louise
Mucker, Eric M.
Johnson, Joshua C.
O'Hearn, Aileen
Bangura, James
Coomber, Moinya
Minogue, Timothy D.
TI Circulating microRNA profiles of Ebola virus infection
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ZAIRE EBOLAVIRUS; SIERRA-LEONE; DISEASE; CLASSIFICATION; EXPRESSION;
SUPPORT; CANCER; TIME; GLYCOPROTEIN; TRANSMISSION
AB Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections.
C1 [Duy, Janice; Koehler, Jeffrey W.; Schoepp, Randal J.; O'Hearn, Aileen; Minogue, Timothy D.] US Army, Med Res Inst Infect Dis, Diagnost Syst Div, Frederick, MD USA.
[Honko, Anna N.; Pitt, M. Louise; Mucker, Eric M.; Johnson, Joshua C.] US Army, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21701 USA.
[Wauquier, Nadia; Bangura, James; Coomber, Moinya] Metabiota, Kenema, Sierra Leone.
[Gonzalez, Jean-Paul] Metabiota, Washington, DC USA.
[Honko, Anna N.; Johnson, Joshua C.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
RP Minogue, TD (reprint author), US Army, Med Res Inst Infect Dis, Diagnost Syst Div, Frederick, MD USA.
EM timothy.d.minogue.civ@mail.mil
OI Honko, Anna/0000-0001-9165-148X; Koehler, Jeffrey/0000-0003-3225-6599
FU Defense Threat Reduction Agency award [CB3630]
FX The authors would like to thank the members of the Virology Division,
Pathology Division and the Center for Aerobiological Sciences at
USAMRIID for study support. Specifically, we would like to thank the
following for their assistance: Heather Esham, Joshua Shamblin, Ginger
Donnelly, Nancy Twenhafel, Dave Dyer and Steve Orr. We would also like
to thank Dr. Christopher Stefan for his assistance. Funding for this
work was provided through Defense Threat Reduction Agency award #CB3630
( awarded to Timothy D. Minogue and Jeffrey W. Koehler). The funders had
no role in study design, data collection and interpretation, or the
decision to submit the work for publication.
NR 69
TC 2
Z9 2
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 21
PY 2016
VL 6
AR 24496
DI 10.1038/srep24496
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ8SR
UT WOS:000374483800001
PM 27098369
ER
PT J
AU Fauci, AS
AF Fauci, Anthony S.
TI A Dual Research Path
SO CELL
LA English
DT Editorial Material
C1 [Fauci, Anthony S.] NIAID, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 21
PY 2016
VL 165
IS 3
BP 510
EP 510
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DK0XW
UT WOS:000374636800003
ER
PT J
AU Swinstead, EE
Miranda, TB
Paakinaho, V
Baek, S
Goldstein, I
Hawkins, M
Karpova, TS
Ball, D
Mazza, D
Lavis, LD
Grimm, JB
Morisaki, T
Grontved, L
Presman, DM
Hager, GL
AF Swinstead, Erin E.
Miranda, Tina B.
Paakinaho, Ville
Baek, Songjoon
Goldstein, Ido
Hawkins, Mary
Karpova, Tatiana S.
Ball, David
Mazza, Davide
Lavis, Luke D.
Grimm, Jonathan B.
Morisaki, Tatsuya
Grontved, Lars
Presman, Diego M.
Hager, Gordon L.
TI Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin
Transitions
SO CELL
LA English
DT Article
ID TRANSCRIPTION FACTOR; GLUCOCORTICOID-RECEPTOR; BREAST-CANCER; IN-VIVO;
BINDING; ESTROGEN; REVEALS; CELLS; ACCESSIBILITY; NUCLEOSOME
AB The estrogen receptor (ER), glucocorticoid receptor (GR), and forkhead box protein 1 (FoxA1) are significant factors in breast cancer progression. FoxA1 has been implicated in establishing ER-binding patterns though its unique ability to serve as a pioneer factor. However, the molecular interplay between ER, GR, and FoxA1 requires further investigation. Here we show that ER and GR both have the ability to alter the genomic distribution of the FoxA1 pioneer factor. Single-molecule tracking experiments in live cells reveal a highly dynamic interaction of FoxA1 with chromatin in vivo. Furthermore, the FoxA1 factor is not associated with detectable footprints at its binding sites throughout the genome. These findings support a model wherein interactions between transcription factors and pioneer factors are highly dynamic. Moreover, at a subset of genomic sites, the role of pioneer can be reversed, with the steroid receptors serving to enhance binding of FoxA1.
C1 [Swinstead, Erin E.; Miranda, Tina B.; Paakinaho, Ville; Baek, Songjoon; Goldstein, Ido; Hawkins, Mary; Karpova, Tatiana S.; Ball, David; Morisaki, Tatsuya; Grontved, Lars; Presman, Diego M.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA.
[Mazza, Davide] Osped San Raffaele, Ist Sci, Ctr Imaging Sperimentale, I-20132 Milan, Italy.
[Mazza, Davide] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
[Lavis, Luke D.; Grimm, Jonathan B.] Howard Hughes Med Inst, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
[Morisaki, Tatsuya] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
[Grontved, Lars] Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
RI Mazza, Davide/R-5340-2016;
OI Mazza, Davide/0000-0003-2776-4142; Lavis, Luke/0000-0002-0789-6343;
Goldstein, Ido/0000-0003-0139-1499; Presman, Diego/0000-0003-4515-8058;
Grontved, Lars/0000-0002-6735-8483
FU NIH, NCI, Center for Cancer Research; Howard Hughes Medical Institute;
Australian Postgraduate Award; National Institute of General Medical
Sciences Pharmacological Research and Training Fellowship; Sigrid
Juselius Foundation; Marie Curie International Incoming Fellowship [GA:
27432]; Japan Society for the Promotion of Science; Danish Research
Council; SDU2020
FX The authors thank the National Cancer Institute Advanced Technology
Program Sequencing Facility for sequencing services. The research was
supported, in part, by the Intramural Research Program of the NIH, NCI,
Center for Cancer Research and the Howard Hughes Medical Institute.
E.E.S. was supported, in part, by an Australian Postgraduate Award.
T.B.M. was supported, in part, by a National Institute of General
Medical Sciences Pharmacological Research and Training Fellowship. V.P.
was supported, in part, by the Sigrid Juselius Foundation. D.M. was
supported, in part, by a Marie Curie International Incoming Fellowship
(GA: 27432). T.M. was supported, in part, by the Japan Society for the
Promotion of Science. L.G. was supported by the Danish Research Council
and SDU2020. The authors declare the following competing financial
interests: J.B.G. and L.D.L. have filed patent applications on the
Janelia Fluor dyes, such as JF549, whose value may be affected by this
publication.
NR 47
TC 15
Z9 15
U1 8
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 21
PY 2016
VL 165
IS 3
BP 593
EP 605
DI 10.1016/j.cell.2016.02.067
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DK0XW
UT WOS:000374636800018
PM 27062924
ER
PT J
AU Velazquez, EJ
Lee, KL
Jones, RH
Al-Khalidi, HR
Hill, JA
Panza, JA
Michler, RE
Bonow, RO
Doenst, T
Petrie, MC
Oh, JK
She, LL
Moore, VL
Desvigne-Nickens, P
Sopko, G
Rouleau, JL
AF Velazquez, Eric J.
Lee, Kerry L.
Jones, Robert H.
Al-Khalidi, Hussein R.
Hill, James A.
Panza, Julio A.
Michler, Robert E.
Bonow, Robert O.
Doenst, Torsten
Petrie, Mark C.
Oh, Jae K.
She, Lilin
Moore, Vanessa L.
Desvigne-Nickens, Patrice
Sopko, George
Rouleau, Jean L.
CA STICHES Investigators
TI Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LEFT-VENTRICULAR DYSFUNCTION; LOW EJECTION FRACTION; FAILURE STICH
TRIAL; HEART-FAILURE; RANDOMIZED-TRIAL; FOLLOW-UP; SURGICAL-TREATMENT;
GRAFT-SURGERY; SURVIVAL-DATA; DISEASE
AB BACKGROUND
The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear.
METHODS
From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years.
RESULTS
A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P = 0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P = 0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test).
CONCLUSIONS
In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone.
C1 [Velazquez, Eric J.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Lee, Kerry L.; Al-Khalidi, Hussein R.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA.
[Jones, Robert H.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[She, Lilin; Moore, Vanessa L.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Hill, James A.] Univ Florida, Gainesville, FL USA.
[Panza, Julio A.] Westchester Med Ctr, Valhalla, NY USA.
[Panza, Julio A.] New York Med Coll, Valhalla, NY 10595 USA.
[Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiothorac & Vasc Surg, New York, NY USA.
[Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Doenst, Torsten] Univ Jena, Univ Hosp Jena, Dept Cardiothorac Surg, Jena, Germany.
[Petrie, Mark C.] Univ Glasgow, Glasgow, Lanark, Scotland.
[Petrie, Mark C.] Golden Jubilee Natl Hosp, Glasgow, Lanark, Scotland.
[Oh, Jae K.] Mayo Clin, Rochester, MN USA.
[Desvigne-Nickens, Patrice; Sopko, George] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
[Rouleau, Jean L.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
RP Velazquez, EJ (reprint author), Duke Clin Res Inst, Rm 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA.
EM eric.velazquez@duke.edu
RI Nicolau, Jose/E-1487-2012
FU National Institutes of Health
FX Funded by the National Institutes of Health; STICH [and STICHES]
ClinicalTrials.gov number, NCT00023595.
NR 28
TC 41
Z9 41
U1 12
U2 16
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 21
PY 2016
VL 374
IS 16
BP 1511
EP 1520
DI 10.1056/NEJMoa1602001
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ7IA
UT WOS:000374383900004
PM 27040723
ER
PT J
AU Rohleder, F
Huang, J
Xue, YT
Kuper, J
Round, A
Seidman, M
Wang, WD
Kisker, C
AF Rohleder, Florian
Huang, Jing
Xue, Yutong
Kuper, Jochen
Round, Adam
Seidman, Michael
Wang, Weidong
Kisker, Caroline
TI FANCM interacts with PCNA to promote replication traverse of DNA
interstrand crosslinks
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MAINTAIN GENOME STABILITY; ARCHAEAL HEF PROTEIN; CELL NUCLEAR ANTIGEN;
ANEMIA CORE COMPLEX; HOMOLOGOUS RECOMBINATION; FLAP ENDONUCLEASE-1;
PYROCOCCUS-FURIOSUS; STRUCTURAL BASIS; REPAIR NETWORK; PATHWAY
AB FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.
C1 [Rohleder, Florian; Kuper, Jochen; Kisker, Caroline] Univ Wurzburg, Inst Biol Struct, Rudolf Virchow Ctr Expt Biomed, D-97080 Wurzburg, Germany.
[Huang, Jing; Seidman, Michael] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Xue, Yutong; Wang, Weidong] NIA, Lab Genet, NIH, Baltimore, MD 21224 USA.
[Round, Adam] European Mol Biol Lab, Grenoble Outstn, 71 Ave Martyrs, F-38042 Grenoble, France.
[Round, Adam] Univ Grenoble Alpes, CNRS, EMBL, Unit Virus Host Cell Interact, 71 Ave Martyrs, F-38042 Grenoble, France.
[Round, Adam] Keele Univ, Fac Nat Sci, Keele ST5 5BG, Staffs, England.
RP Kisker, C (reprint author), Univ Wurzburg, Inst Biol Struct, Rudolf Virchow Ctr Expt Biomed, D-97080 Wurzburg, Germany.; Seidman, M (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.; Wang, WD (reprint author), NIA, Lab Genet, NIH, Baltimore, MD 21224 USA.
EM seidmanm@grc.nia.nih.gov; wangw@grc.nia.nih.gov;
caroline.kisker@virchow.uni-wuerzburg.de
FU Deutsche Forschungsgemeinschaft (DFG) [Forschungszentrum FZ-82];
Intramural Research Program of the National Institute on Aging
[AG000688-07]; National Institute of Health (NIH)
FX Deutsche Forschungsgemeinschaft (DFG) [Forschungszentrum FZ-82 to C.K.];
Intramural Research Program of the National Institute on Aging
[AG000688-07 in part]; National Institute of Health (NIH). Funding for
open access charge: Deutsche Forschungsgemeinschaft (DFG)
[Forschungszentrum FZ-82 to C.K.]; Intramural Research Program of the
National Institute on Aging [AG000688-07 in part]; National Institute of
Health (NIH).
NR 66
TC 2
Z9 2
U1 4
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 20
PY 2016
VL 44
IS 7
BP 3219
EP 3232
DI 10.1093/nar/gkw037
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7DM
UT WOS:000375800200030
PM 26825464
ER
PT J
AU Govindaraju, A
Cortez, JD
Reveal, B
Christensen, SM
AF Govindaraju, Aruna
Cortez, Jeremy D.
Reveal, Brad
Christensen, Shawn M.
TI Endonuclease domain of non-LTR retrotransposons: loss-of-function
mutants and modeling of the R2Bm endonuclease
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID II RESTRICTION ENDONUCLEASES; PRIMED-REVERSE-TRANSCRIPTION; HOLLIDAY
JUNCTION RESOLVASE; BOMBYX-MORI; RNA GENES; EVOLUTIONARY RELATIONSHIP;
DROSOPHILA-MELANOGASTER; ECORV ENDONUCLEASE; CRYSTAL-STRUCTURE; DNA
RECOGNITION
AB Non-LTR retrotransposons are an important class of mobile elements that insert into host DNA by target-primed reverse transcription (TPRT). Non-LTR retrotransposons must bind to theirm RNA, recognize and cleave their target DNA, and perform TPRT at the site of DNA cleavage. As DNA binding and cleavage are such central parts of the integration reaction, a better understanding of the endonuclease encoded by non-LTR retrotransposons is needed. This paper explores the R2 endonuclease domain from Bombyx mori using in vitro studies and in silico modeling. Mutations in conserved sequences located across the putative PD-(D/E)XK endonuclease domain reduced DNA cleavage, DNA binding and TPRT. A mutation at the beginning of the first alpha-helix of the modeled endonuclease obliterated DNA cleavage and greatly reduced DNA binding. It also reduced TPRT when tested on pre-cleaved DNA substrates. The catalytic K was located to a non-canonical position within the second alpha-helix. Amutation located after the fourth beta-strand reduced DNA binding and cleavage. The motifs that showed impaired activity form an extensive basic region. The R2 biochemical and structural data are compared and contrasted with that of two other well characterized PD-(D/E) XK endonucleases, restriction endonucleases and archaeal Holliday junction resolvases.
C1 [Govindaraju, Aruna; Cortez, Jeremy D.; Reveal, Brad; Christensen, Shawn M.] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
[Reveal, Brad] NICHD, NIH, Bethesda, MD 20814 USA.
RP Christensen, SM (reprint author), Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
EM shawnc@uta.edu
FU National Science Foundation [0950983]
FX National Science Foundation [0950983]. Funding for open access charge:
National Science Foundation [0950983].
NR 55
TC 0
Z9 0
U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 20
PY 2016
VL 44
IS 7
BP 3276
EP 3287
DI 10.1093/nar/gkw134
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7DM
UT WOS:000375800200034
PM 26961309
ER
PT J
AU Tsetsarkin, KA
Liu, GP
Shen, K
Pletnev, AG
AF Tsetsarkin, Konstantin A.
Liu, Guangping
Shen, Kui
Pletnev, Alexander G.
TI Kissing-loop interaction between 5 ' and 3 ' ends of tick-borne Langat
virus genome 'bridges the gap' between mosquito- and tick-borne
flaviviruses in mechanisms of viral RNA cyclization: applications for
virus attenuation and vaccine development
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID WEST-NILE-VIRUS; CENTRAL-NERVOUS-SYSTEM; YELLOW-FEVER-VIRUS;
ENCEPHALITIS-VIRUS; DENGUE VIRUS; FUNCTIONAL-ANALYSIS; NONCODING REGION;
NEURONAL DIFFERENTIATION; UNTRANSLATED REGION; RHESUS-MONKEYS
AB Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective pressure, restricting their use in vaccine development. To overcome this limitation, we developed a new approach for miRNA-targeting of tick-borne flavivirus (Langat virus, LGTV) in the duplicated capsid gene region (DCGR). Genetic stability of viruses with DCGR was ensured by the presence of multiple cis-acting elements within the N-terminal capsid coding region, including the stem-loop structure (5' SL6) at the 3' end of the promoter. We found that the 5'SL6 functions as a structural scaffold for the conserved hexanucleotide motif at its tip and engages in a complementary interaction with the region present in the 3' NCR to enhance viral RNA replication. The resulting kissing-loop interaction, common in tick-borne flaviviruses, supports a single pair of cyclization elements (CYC) and functions as a homolog of the second pair of CYC that is present in the majority of mosquito-borne flaviviruses. Placing miRNA targets into the DCGR results in superior attenuation of LGTV in the CNS and does not interfere with development of protective immunity in immunized mice.
C1 [Tsetsarkin, Konstantin A.; Liu, Guangping; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Shen, Kui] NIAID, Bioinformat & Computat Biosci Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM apletnev@niaid.nih.gov
FU Division of Intramural Research Program of the National Institute of
Allergy and Infectious Diseases; National Institutes of Health
FX Division of Intramural Research Program of the National Institute of
Allergy and Infectious Diseases; National Institutes of Health. Funding
for open access charge: Division of Intramural Research Program of the
National Institute of Allergy and Infectious Diseases; National
Institutes of Health.
NR 64
TC 1
Z9 1
U1 5
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 20
PY 2016
VL 44
IS 7
BP 3330
EP 3350
DI 10.1093/nar/gkw061
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7DM
UT WOS:000375800200038
PM 26850640
ER
PT J
AU Ognjenovic, J
Wu, J
Matthies, D
Baxa, U
Subramaniam, S
Ling, JQ
Simonovic, M
AF Ognjenovic, Jana
Wu, Jiang
Matthies, Doreen
Baxa, Ulrich
Subramaniam, Sriram
Ling, Jiqiang
Simonovic, Miljan
TI The crystal structure of human GlnRS provides basis for the development
of neurological disorders
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRANSFER-RNA-SYNTHETASE; SPINAL-CORD INVOLVEMENT; MARIE-TOOTH-DISEASE;
PONTOCEREBELLAR HYPOPLASIA; BRAIN-STEM; PERRAULT SYNDROME; HEARING-LOSS;
MUTATIONS; GENE; EVOLUTION
AB Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases.
C1 [Ognjenovic, Jana; Simonovic, Miljan] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Wu, Jiang; Ling, Jiqiang] Univ Texas Hlth Sci Ctr Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
[Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Simonovic, M (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.; Ling, JQ (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
EM Jiqiang.ling@uth.tmc.edu; msimon5@uic.edu
OI Simonovic, Miljan/0000-0002-1576-2222; Ling, Jiqiang/0000-0003-4466-8304
FU U.S. DOE [DE-AC02-06CH11357]; Michigan Economic Development Corporation;
Michigan Technology Tri-Corridor [085P1000817]; NCI [ACB-12002]; NIGMS
[AGM-12006]; National Institute of General Medical Sciences (NIGMS) of
the National Institutes of Health (NIH) [R01 GM115431]; startup fund
from The University of Texas, Health Science Center at Houston; NIGMS;
NIH
FX Advanced Photon Source was supported by the U.S. DOE
[DE-AC02-06CH11357]. The LS-CAT Sector 21 was supported by the Michigan
Economic Development Corporation and the Michigan Technology
Tri-Corridor [085P1000817]. The GM/CA@APS sector has been funded from
the NCI [ACB-12002] and NIGMS [AGM-12006]. Kinetic analyses were
supported by the National Institute of General Medical Sciences (NIGMS)
of the National Institutes of Health (NIH) [R01 GM115431 to J.L.] and a
startup fund from The University of Texas, Health Science Center at
Houston [to J.L.]. The structure determination was supported by the
grant from NIGMS [to M.S.]. Funding for open access charge: NIH.
NR 56
TC 1
Z9 1
U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 20
PY 2016
VL 44
IS 7
BP 3420
EP 3431
DI 10.1093/nar/gkw082
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7DM
UT WOS:000375800200044
PM 26869582
ER
PT J
AU Kim, J
Sturgill, D
Tran, AD
Sinclair, DA
Oberdoerffer, P
AF Kim, Jeongkyu
Sturgill, David
Tran, Andy D.
Sinclair, David A.
Oberdoerffer, Philipp
TI Controlled DNA double-strand break induction in mice reveals post-damage
transcriptome stability
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID INFLAMMATORY CYTOKINE SECRETION; RADIATION-INDUCED APOPTOSIS; LIFE-SPAN;
CELLULAR SENESCENCE; HEMATOPOIETIC STEM; INVERTED REPEATS;
GENE-EXPRESSION; I-PPOI; REPAIR; CHROMATIN
AB DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at similar to 140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day course of continuous DSB formation and repair in mouse lymphocytes in vivo. Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction.
C1 [Kim, Jeongkyu; Sturgill, David; Tran, Andy D.; Oberdoerffer, Philipp] NCI, Lab Receptor Biol & Gene Express, 41 Lib Dr, Bethesda, MD 20892 USA.
[Sinclair, David A.] Harvard Univ, Sch Med, Dept Genet, Paul F Glenn Labs Biol Mech Aging, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
RP Oberdoerffer, P (reprint author), NCI, Lab Receptor Biol & Gene Express, 41 Lib Dr, Bethesda, MD 20892 USA.
EM Philipp.Oberdoerffer@nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
NCI; Center for Cancer Research
FX Intramural Research Program of the National Institutes of Health (NIH);
NCI; Center for Cancer Research. Funding for open access charge:
Intramural Research Program of the National Institutes of Health (NIH);
NCI; Center for Cancer Research.
NR 60
TC 2
Z9 2
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 20
PY 2016
VL 44
IS 7
AR e64
DI 10.1093/nar/gkv1482
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7DM
UT WOS:000375800200004
PM 26687720
ER
PT J
AU Singh, NS
Rutkowska, E
Plazinska, A
Khadeer, M
Moaddel, R
Jozwiak, K
Bernier, M
Wainer, IW
AF Singh, Nagendra S.
Rutkowska, Ewelina
Plazinska, Anita
Khadeer, Mohammed
Moaddel, Ruin
Jozwiak, Krzysztof
Bernier, Michel
Wainer, Irving W.
TI Ketamine Metabolites Enantioselectively Decrease Intracellular D-Serine
Concentrations in PC-12 Cells
SO PLOS ONE
LA English
DT Article
ID MAMMALIAN TARGET; NMDA RECEPTORS; CO-AGONISTS; RACEMASE; RELEASE;
NORKETAMINE; ANTAGONISTS; INHIBITION; GABAPENTIN; ACTIVATION
AB D-Serine is an endogenous NMDA receptor co-agonist that activates synaptic NMDA receptors modulating neuronal networks in the cerebral cortex and plays a key role in long-term potentiation of synaptic transmission. D-serine is associated with NMDA receptor neurotoxicity and neurodegeneration and elevated D-serine concentrations have been associated with Alzheimer's and Parkinsons' diseases and amyotrophic lateral sclerosis. Previous studies have demonstrated that the ketamine metabolites (rac)-dehydronorketamine and (2S, 6S)-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells. In the current study, PC-12 cells were incubated with a series of ketamine metabolites and the IC50 values associated with attenuated intracellular D-serine concentrations were determined. The results demonstrate that structural and stereochemical features of the studied compounds contribute to the magnitude of the inhibitory effect with (2S, 6S)-hydroxynorketamine and (2R, 6R)-hydroxynorketamine displaying the most potent inhibition with IC50 values of 0.18 +/- 0.04 nM and 0.68 +/- 0.09 nM. The data was utilized to construct a preliminary 3D-QSAR/pharmacophore model for use in the design of new and more efficient modulators of D-serine.
C1 [Singh, Nagendra S.; Khadeer, Mohammed; Moaddel, Ruin; Wainer, Irving W.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
[Rutkowska, Ewelina; Plazinska, Anita; Jozwiak, Krzysztof] Med Univ Lublin, Dept Biopharm, Lublin, Poland.
[Bernier, Michel] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Wainer, IW (reprint author), NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
EM iwwainer@gmail.com
RI Singh, Nagendra/K-8966-2015;
OI Plazinska, Anita/0000-0002-3698-2574
FU Intramural Research Programs of the National Institute on Aging;
Foundation for Polish Science [2009 - 4/5]
FX The work was funded by the Intramural Research Programs of the National
Institute on Aging and by The Foundation for Polish Science (TEAM
Programme 2009 - 4/5).
NR 32
TC 0
Z9 0
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 20
PY 2016
VL 11
IS 4
AR e0149499
DI 10.1371/journal.pone.0149499
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ9OU
UT WOS:000374543600001
PM 27096720
ER
PT J
AU Xu, JH
Wu, XS
Sheng, JS
Zhang, Z
Yue, HY
Sun, LX
Sgobio, C
Lin, X
Peng, SY
Jin, YH
Gan, L
Cai, HB
Wu, LG
AF Xu, Jianhua
Wu, Xin-Sheng
Sheng, Jiansong
Zhang, Zhen
Yue, Hai-Yuan
Sun, Lixin
Sgobio, Carmelo
Lin, Xian
Peng, Shiyong
Jin, Yinghui
Gan, Lin
Cai, Huaibin
Wu, Ling-Gang
TI alpha-Synuclein Mutation Inhibits Endocytosis at Mammalian Central Nerve
Terminals
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE alpha-synuclein; endocytosis; nerve terminal; Parkinson's disease;
transmitter; vesicle
ID SYNAPTIC-VESICLE ENDOCYTOSIS; PARKINSONS-DISEASE; MEMBRANE CURVATURE;
SLOW ENDOCYTOSIS; MOTOR-NEURONS; CSP-ALPHA; CALCIUM; EXPRESSION;
NEURODEGENERATION; SYNAPTOBREVIN
AB alpha-Synuclein (alpha-syn) missense and multiplication mutations have been suggested to cause neurodegenerative diseases, including Parkinson's disease (PD) and dementia with Lewy bodies. Before causing the progressive neuronal loss, alpha-syn mutations impair exocytosis, which may contribute to eventual neurodegeneration. To understand how alpha-syn mutations impair exocytosis, we developed a mouse model that selectively expressed PD-related human alpha-syn A53T (h-alpha-syn(A53T)) mutation at the calyx of Held terminals, where release mechanisms can be dissected with a patch-clamping technique. With capacitance measurement of endocytosis, we reported that h-alpha-syn(A53T), either expressed transgenically or dialyzed in the short term in calyces, inhibited two of the most common forms of endocytosis, the slow and rapid vesicle endocytosis at mammalian central synapses. The expression of h-alpha-syn(A53T) in calyces also inhibited vesicle replenishment to the readily releasable pool. These findings may help to understand how alpha-syn mutations impair neurotransmission before neurodegeneration.
C1 [Xu, Jianhua; Yue, Hai-Yuan] Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA.
[Wu, Xin-Sheng; Sheng, Jiansong; Zhang, Zhen; Peng, Shiyong; Jin, Yinghui; Wu, Ling-Gang] NINDS, NIH, Bethesda, MD 20892 USA.
[Sun, Lixin; Sgobio, Carmelo; Lin, Xian; Cai, Huaibin] NIA, NIH, Bethesda, MD 20892 USA.
[Gan, Lin] Univ Rochester, Sch Med & Dent, Flaum Eye Inst, Rochester, NY 14642 USA.
RP Xu, JH (reprint author), Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA.; Cai, HB (reprint author), NIA, NIH, Bethesda, MD 20892 USA.
EM jxu1@gru.edu; caih@mail.nih.gov
FU National Institute of Neurological Disorders; National Institute on
Aging [AG-000929, AG-000928]; National Institutes of Health
[1R01-NS-082759]
FX This work was supported by the intramural research programs of the
National Institute of Neurological Disorders and the National Institute
on Aging ( Grants AG-000929 and AG-000928, to H. C.), and the extramural
program of National Institutes of Health ( Grant 1R01-NS-082759).
NR 44
TC 0
Z9 0
U1 1
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 20
PY 2016
VL 36
IS 16
BP 4408
EP 4414
DI 10.1523/JNEUROSCI.3627-15.2016
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DK7UA
UT WOS:000375130000002
PM 27098685
ER
PT J
AU Miller, CT
Freiwald, WA
Leopold, DA
Mitchell, JF
Silva, AC
Wang, XQ
AF Miller, Cory T.
Freiwald, Winrich A.
Leopold, David A.
Mitchell, Jude F.
Silva, Afonso C.
Wang, Xiaoqin
TI Marmosets: A Neuroscientific Model of Human Social Behavior
SO NEURON
LA English
DT Review
ID PRIMATE AUDITORY-CORTEX; VENTROLATERAL PREFRONTAL CORTEX; FACIAL
EXPRESSION RECOGNITION; AUTISM SPECTRUM DISORDER; FACE-PROCESSING
SYSTEM; SCENT-MARKING BEHAVIOR; CALLITHRIX-JACCHUS; COMMON MARMOSETS;
RHESUS MACAQUES; MONKEY AMYGDALA
AB The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species' reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets' behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets' social behavior and cognition are more similar to that of humans. For example, marmosets are among only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this Primer, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and signaling. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in neuropsychiatric disorders.
C1 [Miller, Cory T.] Univ Calif San Diego, Cort Syst & Behav Lab, 9500 Gilman Dr, La Jolla, CA 92093 USA.
[Freiwald, Winrich A.] Rockefeller Univ, Lab Neural Syst, 1230 York Ave, New York, NY 10065 USA.
[Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
[Mitchell, Jude F.] Univ Rochester, Dept Brain & Cognit Sci, 358 Meliora Hall, Rochester, NY 14627 USA.
[Silva, Afonso C.] NINDS, Sect Cerebral Microcirculat, Lab Funct & Mol Imaging, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
[Wang, Xiaoqin] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Lab Auditory Neurophysiol, 720 Rutland Ave, Baltimore, MD 21205 USA.
RP Miller, CT (reprint author), Univ Calif San Diego, Cort Syst & Behav Lab, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM corymiller@ucsd.edu
OI Leopold, David/0000-0002-1345-6360
FU NIH [R01 DC012087, R21 MH104756, U01 NS094330, R01 DC03180, R01
DC005808]; N.S.F. [IDBR 1254309]; Simons Collaboration on the Global
Brain; New York Stem Cell Foundation; Intramural Research Program of the
NIMH [ZIA MH002898, ZIA MH002838]; NSF [INSPIRE Track 2 DBI-1343174];
Intramural Research Program of the NIH, NINDS
FX We thank Ed Connor, Nicho Hatsopoulos, Eric Knudsen, and Jitendra Sharma
for helpful comments on previous versions of this manuscript. C.T.M. was
supported by grants from the NIH (R01 DC012087 and R21 MH104756) and
N.S.F. (IDBR 1254309). V.A.F. was supported by The Simons Collaboration
on the Global Brain, NSF (INSPIRE Track 2 DBI-1343174), and the New York
Stem Cell Foundation. D.A.L. was supported (in part) by the Intramural
Research Program of the NIMH under ZIA MH002898 and ZIA MH002838. J.F.M.
was supported by grants from the NIH (R21 MH104756, U01 NS094330).
A.C.S. was supported by the Intramural Research Program of the NIH,
NINDS. X.W. was supported by grants from the NIH (R01 DC03180 and R01
DC005808).
NR 241
TC 18
Z9 18
U1 13
U2 37
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD APR 20
PY 2016
VL 90
IS 2
BP 219
EP 233
DI 10.1016/j.neuron.2016.03.018
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA DJ8ZV
UT WOS:000374504400006
PM 27100195
ER
PT J
AU De Ravin, SS
Wu, XL
Moir, S
Anaya-O'Brien, S
Kwatemaa, N
Littel, P
Theobald, N
Choi, U
Su, L
Marquesen, M
Hilligoss, D
Lee, J
Buckner, CM
Zarember, KA
O'Connor, G
McVicar, D
Kuhns, D
Throm, RE
Zhou, S
Notarangelo, LD
Hanson, IC
Cowan, MJ
Kang, E
Hadigan, C
Meagher, M
Gray, JT
Sorrentino, BP
Malech, HL
AF De Ravin, Suk See
Wu, Xiaolin
Moir, Susan
Anaya-O'Brien, Sandra
Kwatemaa, Nana
Littel, Patricia
Theobald, Narda
Choi, Uimook
Su, Ling
Marquesen, Martha
Hilligoss, Dianne
Lee, Janet
Buckner, Clarissa M.
Zarember, Kol A.
O'Connor, Geraldine
McVicar, Daniel
Kuhns, Douglas
Throm, Robert E.
Zhou, Sheng
Notarangelo, Luigi D.
Hanson, I. Celine
Cowan, Mort J.
Kang, Elizabeth
Hadigan, Coleen
Meagher, Michael
Gray, John T.
Sorrentino, Brian P.
Malech, Harry L.
TI Lentiviral hematopoietic stem cell gene therapy for X-linked severe
combined immunodeficiency
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; VECTOR INTEGRATION; SCID-X1;
TRANSPLANTATION; DEFICIENCY; ACTIVATION; EXPRESSION; TARGETS; LISTS
AB X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (gamma c) of several interleukin receptors. Gammaretroviral (gamma RV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector gamma c transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.
C1 [De Ravin, Suk See; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Marquesen, Martha; Hilligoss, Dianne; Lee, Janet; Zarember, Kol A.; Kang, Elizabeth; Malech, Harry L.] NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wu, Xiaolin; Su, Ling; Kuhns, Douglas] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Res Technol Program, Frederick, MD 21702 USA.
[Moir, Susan; Buckner, Clarissa M.; Hadigan, Coleen] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[O'Connor, Geraldine; McVicar, Daniel] Natl Canc Inst Frederick, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Throm, Robert E.; Zhou, Sheng; Meagher, Michael; Sorrentino, Brian P.] St Jude Childrens Res Hosp, Dept Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Notarangelo, Luigi D.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Hanson, I. Celine] Texas Childrens Hosp, Houston, TX 77030 USA.
[Cowan, Mort J.] Benioff Childrens Hosp, Dept Pediat, San Francisco, CA USA.
[Cowan, Mort J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gray, John T.] Audentes Therapeut, San Francisco, CA 94101 USA.
RP De Ravin, SS; Malech, HL (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sderavin@niaid.nih.gov; hmalech@niaid.nih.gov
FU Intramural Research Program of NIAID, NIH [Z01-A1-00644, Z01-A1-00988];
National Heart, Lung, and Blood Institute [P01HL 53749]; NIH-NIAID [U54
AI 082973]; Frederick National Laboratory for Cancer Research, NIH
[HHSN261200800001E]; ASSISI Foundation of Memphis
FX This research was supported by the Intramural Research Program of NIAID,
NIH (intramural project numbers Z01-A1-00644 and Z01-A1-00988), and the
National Heart, Lung, and Blood Institute (grant P01HL 53749) and
NIH-NIAID Grant U54 AI 082973. This project has been funded in part with
federal funds from the Frederick National Laboratory for Cancer
Research, NIH, under contract HHSN261200800001E (X.W. and L.S.), and the
ASSISI Foundation of Memphis. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services nor does the mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
Replication-competent viruses assay was performed by the National Gene
Vector Biorepository, Indiana University.
NR 32
TC 13
Z9 13
U1 10
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 20
PY 2016
VL 8
IS 335
AR 335ra57
DI 10.1126/scitranslmed.aad8856
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DJ7SM
UT WOS:000374412300006
PM 27099176
ER
PT J
AU Perovanovic, J
Dell'Orso, S
Gnochi, VF
Jaiswal, JK
Sartorelli, V
Vigouroux, C
Mamchaoui, K
Mouly, V
Bonne, G
Hoffman, EP
AF Perovanovic, Jelena
Dell'Orso, Stefania
Gnochi, Viola F.
Jaiswal, Jyoti K.
Sartorelli, Vittorio
Vigouroux, Corinne
Mamchaoui, Kamel
Mouly, Vincent
Bonne, Gisele
Hoffman, Eric P.
TI Laminopathies disrupt epigenomic developmental programs and cell fate
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID NUCLEAR LAMINA INTERACTIONS; EMBRYONIC STEM-CELLS; PARTIAL
LIPODYSTROPHY; ADIPOCYTE DIFFERENTIATION; MUSCULAR-DYSTROPHIES; MUSCLE
REGENERATION; A/C EXPRESSION; MYOD PATHWAYS; HUMAN GENOME; MOUSE
AB The nuclear envelope protein lamin A is encoded by the lamin A/C (LMNA) gene, which can contain missense mutations that cause Emery-Dreifuss muscular dystrophy (EDMD) (p.R453W). We fused mutated forms of the lamin A protein to bacterial DNA adenine methyltransferase (Dam) to define euchromatic-heterochromatin (epigenomic) transitions at the nuclear envelope during myogenesis (using DamID-seq). Lamin A missense mutations disrupted appropriate formation of lamin A-associated heterochromatin domains in an allele-specific manner-findings that were confirmed by chromatin immunoprecipitation-DNA sequencing (ChIP-seq) in murine H2K cells and DNA methylation studies in fibroblasts from muscular dystrophy patient who carried a distinct LMNA mutation (p.H222P). Observed perturbations of the epigenomic transitions included exit from pluripotency and cell cycle programs [ euchromatin (open, transcribed) to heterochromatin (closed, silent)], as well as induction of myogenic loci (heterochromatin to euchromatin). In muscle biopsies from patients with either a gain- or change-of-function LMNA gene mutation or a loss-of-function mutation in the emerin gene, both of which cause EDMD, we observed inappropriate loss of heterochromatin formation at the Sox2 pluripotency locus, which was associated with persistent mRNA expression of Sox2. Overexpression of Sox2 inhibited myogenic differentiation in human immortalized myoblasts. Our findings suggest that nuclear envelopathies are disorders of developmental epigenetic programming that result from altered formation of lamina-associated domains.
C1 [Perovanovic, Jelena; Gnochi, Viola F.; Jaiswal, Jyoti K.; Hoffman, Eric P.] Childrens Natl Med Ctr, Ctr Genet Med Res, Washington, DC 20010 USA.
[Perovanovic, Jelena; Jaiswal, Jyoti K.; Hoffman, Eric P.] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20010 USA.
[Dell'Orso, Stefania; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Rockville, MD 20852 USA.
[Vigouroux, Corinne] Hop St Antoine, AP HP, Lab Commun Biol & Genet Mol, F-75012 Paris, France.
[Vigouroux, Corinne] INSERM, Ctr Rech St Antoine, UMR S938, F-75012 Paris, France.
[Vigouroux, Corinne] Univ Paris 06, Sorbonne Univ, UMR S938, F-75005 Paris, France.
[Vigouroux, Corinne] ICAN Inst Cardiometab & Nutr, F-75013 Paris, France.
[Mamchaoui, Kamel; Mouly, Vincent; Bonne, Gisele] Univ Paris 06, Sorbonne Univ, INSERM UMRS974, Ctr Res Myol,CNRS FRE3617, F-75013 Paris, France.
[Hoffman, Eric P.] SUNY Binghamton, Sch Pharm, 4400 Vestal Pkwy East, Binghamton, NY 13902 USA.
RP Hoffman, EP (reprint author), Childrens Natl Med Ctr, Ctr Genet Med Res, Washington, DC 20010 USA.; Hoffman, EP (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20010 USA.
EM ehoffman@binghamton.edu
RI Bonne, Gisele/G-3121-2013; Jaiswal, Jyoti/M-5891-2013
OI Jaiswal, Jyoti/0000-0002-5992-5185
FU U.S. NIH [3R01 NS29525]; Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases;
Association Francaise contre les Myopathies (A.F.M.)
FX This work was supported by the U.S. NIH (grant 3R01 NS29525), the
Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, and the Association Francaise contre
les Myopathies (A.F.M.).
NR 36
TC 1
Z9 1
U1 2
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 20
PY 2016
VL 8
IS 335
AR 335ra58
DI 10.1126/scitranslmed.aad4991
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DJ7SM
UT WOS:000374412300007
PM 27099177
ER
PT J
AU Lee, SM
Backenroth, D
Cheung, YKK
Hershman, DL
Vulih, D
Anderson, B
Ivy, P
Minasian, L
AF Lee, Shing M.
Backenroth, Daniel
Cheung, Ying Kuen Ken
Hershman, Dawn L.
Vulih, Diana
Anderson, Barry
Ivy, Percy
Minasian, Lori
TI Case Example of Dose Optimization Using Data From Bortezomib
Dose-Finding Clinical Trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MOLECULARLY TARGETED AGENTS; PHASE-I TRIAL; OF-THE-LITERATURE;
PROTEASOME INHIBITOR; LIMITING TOXICITY; ADVANCED MALIGNANCIES;
ANTICANCER DRUGS; ADVANCED CANCER; COMBINATION; CARBOPLATIN
AB Purpose
The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose.
Patients and Methods
We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib.
Results
A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was >50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%.
Conclusions
When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. (C) 2016 by American Society of Clinical Oncology
C1 [Lee, Shing M.; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.] Columbia Univ, New York, NY 10032 USA.
[Vulih, Diana; Anderson, Barry] Theradex Syst, Princeton, NJ USA.
[Ivy, Percy; Minasian, Lori] NCI, Bethesda, MD 20892 USA.
RP Lee, SM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, 722 W 168th St,6th Fl, New York, NY 10032 USA.
EM sml2114@columbia.edu
FU American Cancer Society [MRSG-13-146-01-CPHPS]; National Center for
Advancing Translational Sciences, National Institutes of Health [UL1
TR000040]
FX Supported in part by Grant No. MRSG-13-146-01-CPHPS from the American
Cancer Society and by Grant No. UL1 TR000040 from the National Center
for Advancing Translational Sciences, National Institutes of Health.
NR 30
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 20
PY 2016
VL 34
IS 12
BP 1395
EP +
DI 10.1200/JCO.2015.66.0662
PG 8
WC Oncology
SC Oncology
GA DJ6PJ
UT WOS:000374335100020
PM 26926682
ER
PT J
AU Lombardi, F
Herrmann, HJ
Plenz, D
de Arcangelis, L
AF Lombardi, F.
Herrmann, H. J.
Plenz, D.
de Arcangelis, L.
TI Temporal correlations in neuronal avalanche occurrence
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CORTICAL-NEURONS; SPINAL-CORD; STATISTICAL-ANALYSIS; NETWORK DEPRESSION;
BRAIN ACTIVITY; VISUAL-CORTEX; IN-VITRO; TIME; DYNAMICS; VARIABILITY
AB Ongoing cortical activity consists of sequences of synchronized bursts, named neuronal avalanches, whose size and duration are power law distributed. These features have been observed in a variety of systems and conditions, at all spatial scales, supporting scale invariance, universality and therefore criticality. However, the mechanisms leading to burst triggering, as well as the relationship between bursts and quiescence, are still unclear. The analysis of temporal correlations constitutes a major step towards a deeper understanding of burst dynamics. Here, we investigate the relation between avalanche sizes and quiet times, as well as between sizes of consecutive avalanches recorded in cortex slice cultures. We show that quiet times depend on the size of preceding avalanches and, at the same time, influence the size of the following one. Moreover we evidence that sizes of consecutive avalanches are correlated. In particular, we show that an avalanche tends to be larger or smaller than the following one for short or long time separation, respectively. Our analysis represents the first attempt to provide a quantitative estimate of correlations between activity and quiescence in the framework of neuronal avalanches and will help to enlighten the mechanisms underlying spontaneous activity.
C1 [Lombardi, F.; Herrmann, H. J.] ETH, Inst Computat Phys Engn Mat, Zurich, Switzerland.
[Herrmann, H. J.] Univ Fed Ceara, Dept Fis, BR-60451970 Fortaleza, Ceara, Brazil.
[Plenz, D.] NIH, Sect Crit Brain Dynam, Bldg 10, Bethesda, MD 20892 USA.
[de Arcangelis, L.] Univ Naples 2, Dept Ind & Informat Engn, INFN Gr Coll Salerno, Aversa, CE, Italy.
RP Lombardi, F (reprint author), ETH, Inst Computat Phys Engn Mat, Zurich, Switzerland.
EM lombardif00@gmail.com
RI Universidade Federal do Ceara, Physics Department/J-4630-2016; UFC,
DF/E-1564-2017
OI Universidade Federal do Ceara, Physics Department/0000-0002-9247-6780;
FU SNF [205321-138074]; European Research Council (ERC) Advanced Grant
[FP7-319968-FlowCCS]; Intramural Research Program of the National
Institute of Mental Health
FX We acknowledge financial support from the SNF project 205321-138074 and
the European Research Council (ERC) Advanced Grant FP7-319968-FlowCCS.
This study was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 57
TC 1
Z9 1
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 20
PY 2016
VL 6
AR 24690
DI 10.1038/srep24690
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7FS
UT WOS:000374377900001
PM 27094323
ER
PT J
AU Wang, YF
Liu, JY
Ying, XH
Lin, PC
Zhou, BHP
AF Wang, Yifan
Liu, Jingyi
Ying, Xuhua
Lin, Pengnian Charles
Zhou, Binhua P.
TI Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor
Cell Invasion via Inhibition of Hippo Pathway
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CANCER CELLS; YAP PATHWAY; SNAIL; METASTASIS; RECEPTOR; PAR1; MIGRATION;
PHOSPHORYLATION; TUMORIGENESIS; ADHESION
AB Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular dedifferentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated EMT.
C1 [Wang, Yifan; Ying, Xuhua] Zhejiang Acad Chinese Med, Canc Inst Integrat Med, Hangzhou 310007, Zhejiang, Peoples R China.
[Liu, Jingyi] Chinese Acad Med Sci, State Key Lab Expt Hematol, Inst Hematol & Blood Dis Hosp, Tianjin 300020, Peoples R China.
[Liu, Jingyi] Peking Union Med Coll, Tianjin 300020, Peoples R China.
[Liu, Jingyi; Lin, Pengnian Charles] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Wang, Yifan; Liu, Jingyi; Zhou, Binhua P.] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA.
[Wang, Yifan; Liu, Jingyi; Zhou, Binhua P.] Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY 40506 USA.
RP Zhou, BHP (reprint author), Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40506 USA.; Zhou, BHP (reprint author), Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY 40506 USA.
EM peter.zhou@uky.edu
FU NIH [RO1s CA125454, CA188118]; DOD Breakthrough Award [BC140733P1]; Mary
Kay Ash Foundation; National Natural Science Foundation of China
[81402434, 81402432]; Zhejiang Provincial Natural Science Foundation of
China [LQ14H280002]
FX We thank Cathy Anthony for critical reading and editing of this
manuscript. We also thank Dr. Kunliang Guan for providing CTGF-Luc
plasmid for this study. This work was supported in part by grants from
NIH (RO1s CA125454 and CA188118), DOD Breakthrough Award (BC140733P1),
Mary Kay Ash Foundation (to B.P. Zhou), National Natural Science
Foundation of China (No. 81402434 to Y. Wang, and No. 81402432 to J.
Liu), and the Zhejiang Provincial Natural Science Foundation of China
(No. LQ14H280002) (to Y. Wang).
NR 29
TC 4
Z9 5
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 20
PY 2016
VL 6
AR 24606
DI 10.1038/srep24606
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7FK
UT WOS:000374377100001
PM 27094683
ER
PT J
AU Nash, SD
Katamba, A
Mafigiri, DK
Mbulaiteye, SM
Sethi, AK
AF Nash, Scott D.
Katamba, Achilles
Mafigiri, David Kaawa
Mbulaiteye, Sam M.
Sethi, Ajay K.
TI Sex-related alcohol expectancies and high-risk sexual behaviour among
drinking adults in Kampala, Uganda
SO GLOBAL PUBLIC HEALTH
LA English
DT Article
DE Alcohol-related expectancies; high-risk sexual behaviour; HIV; AIDS;
Uganda
ID TOWN SOUTH-AFRICA; CAPE-TOWN; BINGE DRINKING; HIV-INFECTION; CONDOM USE;
WOMEN; CONSUMPTION; MEN; ADOLESCENTS; HIV/AIDS
AB Alcohol consumption, a risk factor for HIV transmission in sub-Saharan Africa, is considered high in Uganda. A cross sectional study was conducted to determine whether sex-related expectations about the effects of alcohol explain the association between alcohol use and risky sexual behaviours in a population-based sample of adults in Kampala. Associations between alcohol use (current and higher risk drinking) and high-risk sexual behaviours (multiple regular partners and casual sex) were tested. In age-sex-adjusted models, having multiple regular partners was associated with current drinking (odds ratio [OR] = 2.76, 95% confidence intervals [CIs] = 1.15, 6.63) and higher risk drinking (OR = 3.35, 95% CI = 1.28, 8.71). Associations were similar but not statistically significant for having a causal sex partner. Sex-related alcohol outcome expectancy was associated with both alcohol use and high-risk sexual behaviour and attenuated relationships between multiple regular partners and both current drinking (OR = 1.94, 95% CI = 0.57, 6.73) and higher risk drinking (OR = 2.44, 95% CI = 0.68, 8.80). In this setting sexual behaviours related with alcohol consumption were explained, in part, by sex-related expectations about the effects of alcohol. These expectations could be an important component to target in HIV education campaigns.
C1 [Nash, Scott D.] Emory Univ, Carter Ctr, Trachoma Control Program, Atlanta, GA 30322 USA.
[Katamba, Achilles] Makerere Univ, Sch Med, Dept Med, Kampala, Uganda.
[Mafigiri, David Kaawa] Makerere Univ, Sch Social Sci, Ctr Social Sci Res AIDS, Dept Social Work & Social Adm, Kampala, Uganda.
[Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Sethi, Ajay K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
RP Nash, SD (reprint author), Emory Univ, Carter Ctr, Trachoma Control Program, Atlanta, GA 30322 USA.; Sethi, AK (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
EM scott.nash@emory.edu; aksethi@wisc.edu
FU National Institutes of Alcohol Abuse and Alcoholism [AA015488]
FX This study was funded by a grant from the National Institutes of Alcohol
Abuse and Alcoholism [grant number AA015488].
NR 40
TC 1
Z9 1
U1 0
U2 5
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1744-1692
EI 1744-1706
J9 GLOB PUBLIC HEALTH
JI Glob. Public Health
PD APR 20
PY 2016
VL 11
IS 4
BP 449
EP 462
DI 10.1080/17441692.2015.1068824
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG1AC
UT WOS:000371796400005
PM 26315308
ER
PT J
AU Soliman, HH
Minton, SE
Han, HS
Ismail-Khan, R
Neuger, A
Khambati, F
Noyes, D
Lush, R
Chiappori, AA
Roberts, JD
Link, C
Vahanian, NN
Mautino, M
Streicher, H
Sullivan, DM
Antonia, SJ
AF Soliman, Hatem H.
Minton, Susan E.
Han, Hyo Sook
Ismail-Khan, Roohi
Neuger, Anthony
Khambati, Fatema
Noyes, David
Lush, Richard
Chiappori, Alberto A.
Roberts, John D.
Link, Charles
Vahanian, Nicholas N.
Mautino, Mario
Streicher, Howard
Sullivan, Daniel M.
Antonia, Scott J.
TI A Phase I study of indoximod in patients with advanced malignancies
SO ONCOTARGET
LA English
DT Article
DE indoleamine 2,3 dioxygenase; 1-methyl-D-tryptophan; indoximod;
immunomodulator
ID INDOLEAMINE 2,3-DIOXYGENASE IDO; T-CELL; TUMOR-SUPPRESSOR; DENDRITIC
CELLS; TRYPTOPHAN; BIN1; INHIBITION; EXPRESSION; MELANOMA; CANCER
AB Purpose: Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase pathway, which causes tumor-mediated immunosuppression. Primary endpoints were maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced solid tumors. Secondary endpoints included response rates, pharmacokinetics, and immune correlates.
Experimental Design: Our 3+3 phase I trial comprised 10 dose levels (200, 300, 400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day). Inclusion criteria were measurable metastatic solid malignancy, age >= 18 years, and adequate organ/marrow function. Exclusion criteria were chemotherapy <= 3 weeks prior, untreated brain metastases, autoimmune disease, or malabsorption.
Results: In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg once/day, 3 patients previously treated with checkpoint inhibitors developed hypophysitis. Five patients showed stable disease > 6 months. Indoximod plasma AUC and Cmax plateaued above 1200mg. Cmax (similar to 12 mu M at 2000 mg twice/day) occurred at 2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels increased across multiple dose levels.
Conclusions: Indoximod was safe at doses up to 2000 mg orally twice/day. Best response was stable disease > 6 months in 5 patients. Induction of hypophysitis, increased tumor antigen autoantibodies and CRP levels were observed.
C1 [Soliman, Hatem H.; Minton, Susan E.; Han, Hyo Sook; Ismail-Khan, Roohi; Neuger, Anthony; Khambati, Fatema; Noyes, David; Lush, Richard; Chiappori, Alberto A.; Sullivan, Daniel M.; Antonia, Scott J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Roberts, John D.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
[Link, Charles; Vahanian, Nicholas N.; Mautino, Mario] NewLink Genetics Inc, Ames, IA USA.
[Streicher, Howard] NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
RP Soliman, HH (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
EM hatem.soliman@moffitt.org
FU Massey Cancer Center NIH [P30-CA016059]; [HHSN261201100100C]
FX The trial was supported under N01 contract HHSN261201100100C and Massey
Cancer Center NIH grant P30-CA016059.
NR 28
TC 5
Z9 5
U1 4
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 19
PY 2016
VL 7
IS 16
BP 22928
EP 22938
DI 10.18632/oncotarget.8216
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DO3TY
UT WOS:000377705900145
PM 27008709
ER
PT J
AU Liang, Y
Guttman, M
Davenport, TM
Hu, SL
Lee, KK
AF Liang, Yu
Guttman, Miklos
Davenport, Thaddeus M.
Hu, Shiu-Lok
Lee, Kelly K.
TI Probing the Impact of Local Structural Dynamics of Conformational
Epitopes on Antibody Recognition
SO BIOCHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; SMALL-ANGLE
SCATTERING; HUMAN MONOCLONAL-ANTIBODIES; CD4 BINDING-SITE; NEUTRALIZING
HIV-1 ANTIBODIES; EXCHANGE MASS-SPECTRA; TYPE-1 GP120; X-RAY;
HYDROGEN/DEUTERIUM EXCHANGE
AB Antibody antigen interactions are governed by recognition of specific residues and structural complementarity between the antigen epitope and antibody paratope. While X-ray crystallography has provided detailed insights into static conformations of antibody antigen complexes, factors such as conformational flexibility and dynamics, which are not readily apparent in the structures, can also have an impact on the binding event. Here we investigate the contribution of dynamics in the HIV-1 gp120 glycoprotein to antibody recognition of conserved conformational epitopes, including the CD4- and coreceptor-binding sites, and an inner domain site that is targeted by ADCC-active antibodies. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) was used to measure local structural dynamics across a panel of variable loop truncation mutants of HIV-1 gp120, including full-length gp120, Delta V3, Delta V1/V2, and extended core, which includes Delta V1-/V2 and V3 loop truncations. CD4-bound full-length gp120 was also examined as a reference state. HDX-MS revealed a clear trend toward an increased level of order of the conserved subunit core resulting from loop truncation. Combined with biolayer interferometry and enzyme-linked immunosorbent assay measurements of antibody antigen binding, we demonstrate that an increased level of ordering of the subunit core was associated with better recognition by an array of antibodies targeting complex conformational epitopes. These results, provide detailed insight into the influence of structural dynamics on antibody antigen interactions and suggest the importance of characterizing the structural stability of vaccine candidates to improve antibody recognition of complex epitopes.
C1 [Liang, Yu; Guttman, Miklos; Davenport, Thaddeus M.; Lee, Kelly K.] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA.
[Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Davenport, Thaddeus M.] NHLBI, Lab Mol & Cellular Imaging, Bethesda, MD 20814 USA.
RP Lee, KK (reprint author), Univ Washington, Dept Med Chem, Seattle, WA 98195 USA.
EM kklee@uw.edu
FU National Institutes of Health (NIH) [R21-AI112389, R01-GM099989]; Bill
and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery
(CAVD) Grant [OPP1033102]; Structural Molecular Biology Program,
Department of Energy's Office of Biological and Environmental Research,
NIH [P41-GM103393, P41-RR001209]
FX The work was supported by National Institutes of Health (NIH) Grants
R21-AI112389 and R01-GM099989 and by Bill and Melinda Gates Foundation
Collaboration for AIDS Vaccine Discovery (CAVD) Grant OPP1033102.
Portions of the work were conducted at SSRL and supported by the
Structural Molecular Biology Program, Department of Energy's Office of
Biological and Environmental Research, NIH Grants P41-GM103393 and
P41-RR001209.
NR 96
TC 1
Z9 1
U1 3
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 19
PY 2016
VL 55
IS 15
BP 2197
EP 2213
DI 10.1021/acs.biochem.5b01354
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK1WX
UT WOS:000374706900001
PM 27003615
ER
PT J
AU LaRochelle, JR
Fodor, M
Xu, X
Durzynska, I
Fan, L
Status, T
Chan, HM
LaMarche, MJ
Chopra, R
Wang, P
Fortin, PD
Acker, MG
Blacklow, SC
AF LaRochelle, Jonathan R.
Fodor, Michelle
Xu, Xiang
Durzynska, Izabela
Fan, Lixin
Status, Travis
Chan, Ho Man
LaMarche, Matthew J.
Chopra, Rajiv
Wang, Ping
Fortin, Pascal D.
Acker, Michael G.
Blacklow, Stephen C.
TI Structural and Functional Consequences of Three Cancer-Associated
Mutations of the Oncogenic Phosphatase SHP2
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN-TYROSINE-PHOSPHATASE; X-RAY-SCATTERING; INSULIN-RECEPTOR
SUBSTRATE-1; ACUTE MYELOID-LEUKEMIA; PTPN11 MUTATIONS; NOONAN-SYNDROME;
MOUSE MODEL; SH-PTP2; DIFFERENTIATION; LEUKEMOGENESIS
AB The proto-oncogene PTPN11 encodes a cytoplasmic protein tyrosine phosphatase, SHP2, which is required for normal development and sustained activation of the Ras-MAPK signaling pathway. Germline mutations in SHP2 cause developmental disorders, and somatic mutations have been identified in childhood and adult cancers and drive leukemia in mice. Despite our knowledge of the PTPN11 variations associated with pathology, the structural and functional consequences of many disease-associated mutants remain poorly understood. Here, we combine X-ray crystallography, small-angle X-ray scattering, and biochemistry to elucidate structural and mechanistic features of three cancer-associated SHP2 variants harboring single point mutations within the N-SH2:PTP interdomain autoinhibitory interface. Our findings directly compare the impact of each mutation on autoinhibition of the phosphatase and advance the development of structure-guided and mutation specific SHP2 therapies.
C1 [LaRochelle, Jonathan R.; Xu, Xiang; Durzynska, Izabela; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[LaRochelle, Jonathan R.; Xu, Xiang; Durzynska, Izabela; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Fodor, Michelle; Status, Travis; Chopra, Rajiv] Novartis Inst Biomed Res, Ctr Prote Chem, Cambridge, MA 02139 USA.
[Chan, Ho Man; Wang, Ping; Fortin, Pascal D.; Acker, Michael G.] Novartis Inst Biomed Res, Oncol, Cambridge, MA 02139 USA.
[LaMarche, Matthew J.] Novartis Inst Biomed Res, Global Discovery Chem, Cambridge, MA 02139 USA.
[Fan, Lixin] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Bas Sci Program, Frederick, MD 21702 USA.
RP Blacklow, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Blacklow, SC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM stephen_blacklow@hms.harvard.edu
FU Novartis-Dana Farber Cancer Institute Drug Development Program [250
GM10718A1]; William Lawrence-Blanche Hughes Foundation; American Cancer
Society [128126]
FX This work was funded in part by the Novartis-Dana Farber Cancer
Institute Drug Development Program, 250 GM10718A1 (X.X. and S.C.B.), and
by the William Lawrence-Blanche Hughes Foundation (to S.C.B.). M.F.,
T.S., H.M.C., M.J.L., RC., P.W., P.D.F., and M.G.A. are employees of
Novartis. J.R.L. gratefully acknowledges postdoctoral fellowship funding
from the American Cancer Society (Award 128126).
NR 39
TC 0
Z9 1
U1 2
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 19
PY 2016
VL 55
IS 15
BP 2269
EP 2277
DI 10.1021/acs.biochem.5b01287
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK1WX
UT WOS:000374706900007
PM 27030275
ER
PT J
AU Platts-Mills, TF
Nicholson, RJ
Richmond, NL
Patel, KV
Simonsick, EM
Domeier, RM
Swor, RA
Hendry, PL
Peak, DA
Rathlev, NK
Jones, JS
Lee, DC
Weaver, MA
Keefe, FJ
McLean, SA
AF Platts-Mills, Timothy F.
Nicholson, Robert J.
Richmond, Natalie L.
Patel, Kushang V.
Simonsick, Eleanor M.
Domeier, Robert M.
Swor, Robert A.
Hendry, Phyllis L.
Peak, David A.
Rathlev, Niels K.
Jones, Jeffrey S.
Lee, David C.
Weaver, Mark A.
Keefe, Francis J.
McLean, Samuel A.
TI Restricted activity and persistent pain following motor vehicle
collision among older adults: a multicenter prospective cohort study
SO BMC GERIATRICS
LA English
DT Article
DE Aged; Motor Activity; Emergency medicine; Pain; Geriatrics; Traffic
accidents
ID LOW-BACK-PAIN; EMERGENCY-DEPARTMENT PATIENTS; PHYSICAL-ACTIVITY SCALE;
UNITED-STATES FINDINGS; 2011 NATIONAL-HEALTH; BED REST; COGNITIVE
IMPAIRMENT; FUNCTIONAL DECLINE; 6-ITEM SCREENER; WHIPLASH INJURY
AB Background: Restricted physical activity commonly occurs following acute musculoskeletal pain in older adults and may influence long-term outcomes. We sought to examine the relationship between restricted physical activity after motor vehicle collision (MVC) and the development of persistent pain.
Methods: We examined data from a prospective study of adults >= 65 years of age presenting to the emergency department (ED) after MVC without life-threatening injuries. Restricted physical activity 6 weeks after MVC was defined in three different ways: 1) by a >= 25 point decrease in Physical Activity Scale in the Elderly (PASE) score, 2) by the answer "yes" to the question, "during the past two weeks, have you stayed in bed for at least half a day?", and 3) by the answer "yes" to the question, "during the past two weeks, have you cut down on your usual activities as compared to before the accident?" We examined relationships between each definition of restricted activity and pain severity, pain interference, and functional capacity at 6 months with adjustment for confounders.
Results: Within the study sample (N = 164), adjusted average pain severity scores at 6 months did not differ between patients with and without restricted physical activity based on decreased PASE score (2.54 vs. 2.07, p = 0.32). In contrast, clinically and statistically important differences in adjusted average pain severity at 6 months were observed for patients who reported spending half a day in bed vs. those who did not (3.56 vs. 1.91, p < 0.01). In adjusted analyses, both decreased PASE score and cutting down on activity were associated with functional capacity at 6 months, but only decreased PASE score was associated with increased ADL difficulty at 6 months (0.70 vs. -0.01, p = 0.02).
Conclusions: Among older adults experiencing MVC, those reporting bed rest or reduced activity 6 weeks after the collision reported higher pain and pain interference scores at 6 months. More research is needed to determine if interventions to promote activity can improve outcomes after MVC in older adults.
C1 [Platts-Mills, Timothy F.; Nicholson, Robert J.; Richmond, Natalie L.] Univ N Carolina, Dept Emergency Med, 170 Manning Dr, Chapel Hill, NC USA.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, 1959 NE Pacific St, Seattle, WA 98195 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Domeier, Robert M.] St Joseph Mercy Hlth Syst, Dept Emergency Med, 5301 McAuley Dr, Ypsilanti, MI USA.
[Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, 3601 W 13 Mile Rd, Royal Oak, MI 48072 USA.
[Hendry, Phyllis L.] Univ Florida, Coll Med Jacksonville, Dept Emergency Med, 1515 SW Archer Rd, Gainesville, FL USA.
[Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA.
[Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, 759 Chestnut St, Springfield, MA USA.
[Jones, Jeffrey S.] Spectrum Hlth, Dept Emergency Med, Butterworth Campus,100 Michigan St NE, Grand Rapids, MI 49503 USA.
[Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, 300 Community Dr, Manhasset, NY USA.
[Weaver, Mark A.] Univ N Carolina, Dept Med, 170 Manning Dr, Chapel Hill, NC USA.
[Keefe, Francis J.] Duke Univ, Dept Psychiat, 17 Chapel Dr, Durham, NC 27706 USA.
[McLean, Samuel A.] Univ N Carolina, Dept Anesthesiol, 170 Manning Dr, Chapel Hill, NC USA.
RP Platts-Mills, TF (reprint author), Univ N Carolina, Dept Emergency Med, 170 Manning Dr, Chapel Hill, NC USA.
EM tplattsm@med.unc.edu
FU National Institute on Aging [K23AG038548]
FX Dr. Platts-Mills is supported by grant K23AG038548 from the National
Institute on Aging. The National Institute on Aging had no role in the
design of the study, the collection, analysis, and interpretation of
data, or the writing of the manuscript.
NR 48
TC 0
Z9 0
U1 6
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2318
J9 BMC GERIATR
JI BMC Geriatr.
PD APR 19
PY 2016
VL 16
AR 86
DI 10.1186/s12877-016-0260-z
PG 11
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK1KK
UT WOS:000374670800003
PM 27094038
ER
PT J
AU Wang, HY
Zhang, X
Xue, L
Xing, J
Jouvin, MH
Putney, JW
Anderson, MP
Trebak, M
Kinet, JP
AF Wang, Huiyun
Zhang, Xuexin
Xue, Li
Xing, Juan
Jouvin, Marie-Helene
Putney, James W.
Anderson, Matthew P.
Trebak, Mohamed
Kinet, Jean-Pierre
TI Low-Voltage-Activated Ca(V)3.1 Calcium Channels Shape T Helper Cell
Cytokine Profiles
SO IMMUNITY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLONY-STIMULATING FACTOR;
GM-CSF; LYMPHOCYTE FUNCTION; CA2+ CHANNELS; EFFECTOR FUNCTIONS;
CYCLOSPORINE-A; MICE LACKING; DIFFERENTIATION; NFAT
AB Activation of T cells is mediated by the engagement of T cell receptors (TCRs) followed by calcium entry via store-operated calcium channels. Here we have shown an additional route for calcium entry into T cells-through the low-voltage-activated T-type Ca(V)3.1 calcium channel. Ca(V)3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for Ca(V)3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells. Ca(V)3.1 deficiency led to decreased secretion of GM-CSF from in vitro polarized Th1 and Th17 cells. Nuclear translocation of the nuclear factor of activated T cell (NFAT) was also reduced in Ca(V)3.1-deficient T cells. These data provide evidence for T-type channels in immune cells and their potential role in shaping the autoimmune response.
C1 [Wang, Huiyun; Xue, Li; Jouvin, Marie-Helene; Anderson, Matthew P.; Kinet, Jean-Pierre] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
[Wang, Huiyun; Xue, Li; Jouvin, Marie-Helene; Anderson, Matthew P.; Kinet, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Zhang, Xuexin; Trebak, Mohamed] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA.
[Xing, Juan; Putney, James W.] NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Anderson, Matthew P.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA.
RP Kinet, JP (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.; Kinet, JP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM jkinet2@me.com
FU NIH [5T32HL789315, HL097111, 5R01NS081916, 5R37GM53950, 1R01AI095308]
FX This work was funded in part by NIH grants 5T32HL789315 to H.W.,
HL097111 to M.T., 5R01NS081916 to M.P.A., and 5R37GM53950 and
1R01AI095308 to J.-P.K.
NR 57
TC 1
Z9 1
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD APR 19
PY 2016
VL 44
IS 4
BP 782
EP 794
DI 10.1016/j.immuni.2016.01.015
PG 13
WC Immunology
SC Immunology
GA DJ8EC
UT WOS:000374444300011
PM 27037192
ER
PT J
AU Kong, L
Ju, B
Chen, YJ
He, LL
Ren, L
Liu, JD
Hong, KX
Su, B
Wang, Z
Ozorowski, G
Ji, XL
Hua, YZ
Chen, YL
Deller, MC
Hao, YL
Feng, Y
Garces, F
Wilson, R
Dai, KF
O'Dell, S
McKee, K
Mascola, JR
Ward, AB
Wyatt, RT
Li, YX
Wilson, IA
Zhu, J
Shao, YM
AF Kong, Leopold
Ju, Bin
Chen, Yajing
He, Linling
Ren, Li
Liu, Jiandong
Hong, Kunxue
Su, Bin
Wang, Zheng
Ozorowski, Gabriel
Ji, Xiaolin
Hua, Yuanzi
Chen, Yanli
Deller, Marc C.
Hao, Yanling
Feng, Yi
Garces, Fernando
Wilson, Richard
Dai, Kaifan
O'Dell, Sijy
McKee, Krisha
Mascola, John R.
Ward, Andrew B.
Wyatt, Richard T.
Li, Yuxing
Wilson, Ian A.
Zhu, Jiang
Shao, Yiming
TI Key gp120 Glycans Pose Roadblocks to the Rapid Development of
VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor
SO IMMUNITY
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; HIV-1 ENVELOPE TRIMER;
HIV-1-NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; CD4-BINDING SITE;
STRUCTURAL BASIS; RATIONAL DESIGN; GLYCOPROTEINS; VACCINE;
IDENTIFICATION
AB VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.
C1 [Kong, Leopold; Ozorowski, Gabriel; Hua, Yuanzi; Garces, Fernando; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Ju, Bin; Ren, Li; Liu, Jiandong; Hong, Kunxue; Wang, Zheng; Ji, Xiaolin; Chen, Yanli; Hao, Yanling; Feng, Yi; Shao, Yiming] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Ctr AIDS STD Control & Prevent, Beijing 102206, Peoples R China.
[Ju, Bin; Ren, Li; Liu, Jiandong; Hong, Kunxue; Wang, Zheng; Ji, Xiaolin; Chen, Yanli; Hao, Yanling; Feng, Yi; Shao, Yiming] Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 102206, Peoples R China.
[Kong, Leopold; Ozorowski, Gabriel; Hua, Yuanzi; Garces, Fernando; Ward, Andrew B.; Wyatt, Richard T.; Wilson, Ian A.; Zhu, Jiang] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.
[Chen, Yajing; He, Linling; Dai, Kaifan; Wyatt, Richard T.; Zhu, Jiang] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Deller, Marc C.] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA.
[Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Kong, Leopold; Ozorowski, Gabriel; Hua, Yuanzi; Garces, Fernando; Wilson, Richard; Ward, Andrew B.; Wyatt, Richard T.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Kong, Leopold; Ozorowski, Gabriel; Hua, Yuanzi; Garces, Fernando; Wilson, Richard; Ward, Andrew B.; Wyatt, Richard T.; Wilson, Ian A.] Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA.
[Su, Bin] Jiangsu Prov Ctr Dis Control & Prevent, Nanjing 210009, Jiangsu, Peoples R China.
[O'Dell, Sijy; McKee, Krisha; Mascola, John R.] NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Li, Yuxing] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
[Shao, Yiming] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China.
[Shao, Yiming] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China.
RP Shao, YM (reprint author), Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Natl Ctr AIDS STD Control & Prevent, Beijing 102206, Peoples R China.; Shao, YM (reprint author), Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 102206, Peoples R China.; Zhu, J (reprint author), Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.; Zhu, J (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.; Shao, YM (reprint author), Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China.; Shao, YM (reprint author), Nankai Univ, Sch Med, Tianjin 300071, Peoples R China.
EM jiang@scripps.edu; yshao@bjmu.edu.cn
RI Ward, Andrew/F-9203-2014
OI Ward, Andrew/0000-0001-7153-3769
FU US Department of Energy, Basic Energy Sciences, Office of Science
[DE-AC02-06CH11357]; National Major projects for Infectious Diseases
Control and Prevention [2012ZX10001008]; International AIDS Vaccine
Initiative Neutralizing Antibody Center; CAVD; Center for HIV/AIDS
Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [UM1 AI100663];
HIV Vaccine Research and Design (HIVRAD) program [P01 AI110657]; Joint
Center of Structural Genomics (JCSG) - NIH NIGMS, Protein Structure
Initiative [U54 GM094586]; SKLID Development grant [2012SKLID103]; NIH
NIAID [R01 AI102766, AI084817]; NIH NIAID development grant from the
Center for AIDS Research at the University of California, San Diego
[P30AI36214]; NIH CIPRA grant [U19AI51915]; American Foundation for AIDS
Research Mathilde Krim Fellowship in Basic Biomedical Research
FX We are very grateful to R. Stanfield for helpful discussions; M.
Elsliger for computer support; H. Tien for crystallization screening; A.
Eroshkin for help with calculating N-linked glycosylation frequencies;
J. Hou, P. Li, and M. Zhu for help with antibody binding assays; D. Li,
H. Liang, and H. Peng for help with measuring patient CD4+ T
cell counts; Q. Zhao for help with viral load assays; J. Wu and X. Ding
for help with patient blood sample collection; and J. P. Verenini for
manuscript formatting. X-ray data sets were collected at the Advanced
Photon Source (APS) beamline 23ID-B. Use of the APS was supported by the
US Department of Energy, Basic Energy Sciences, Office of Science, under
contract no. DE-AC02-06CH11357. Electron microscopy data were collected
at the Scripps Research Institute EM Facility. This work was supported
by the National Major projects for Infectious Diseases Control and
Prevention (2012ZX10001008) (Y. S.), by the International AIDS Vaccine
Initiative Neutralizing Antibody Center and CAVD, by the Center for
HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID UM1
AI100663) (A. B. W., I. A. W., J. Z.), by the HIV Vaccine Research and
Design (HIVRAD) program (P01 AI110657) (A. B. W., I. A. W.), by the
Joint Center of Structural Genomics (JCSG) funded by the NIH NIGMS,
Protein Structure Initiative (U54 GM094586) (I. A. W.), by the SKLID
Development grant (2012SKLID103) (Y. S.), by NIH NIAID grants R01
AI102766 (Y. L.) and AI084817 (I. A. W., A. B. W.), and by an NIH NIAID
development grant from the Center for AIDS Research at the University of
California, San Diego (P30AI36214) (Y. L., J. Z.). A portion of this
work was supported by the NIH CIPRA grant (U19AI51915) (Y. S.) and by an
American Foundation for AIDS Research Mathilde Krim Fellowship in Basic
Biomedical Research (L. K.). Y. S. is grateful to Dennis Burton for
hosting his stay at The Scripps Research Institute to initiate this
collaborative study.
NR 41
TC 11
Z9 11
U1 4
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD APR 19
PY 2016
VL 44
IS 4
BP 939
EP 950
DI 10.1016/j.immuni.2016.03.006
PG 12
WC Immunology
SC Immunology
GA DJ8EC
UT WOS:000374444300023
PM 27067056
ER
PT J
AU Karlawish, J
Kim, SYH
AF Karlawish, Jason
Kim, Scott Y. H.
TI Acute stroke trials without informed consent: Toward an evidence-based
ethical practice
SO NEUROLOGY
LA English
DT Editorial Material
ID THROMBOLYSIS; TIME
AB Progress in treatment requires progress in experiment, and the treatment of acute stroke, along with many other neurologic diseases, needs more human experiments in the form of clinical trials. However, the acuity of the disease, the need for rapid intervention, and the decisional impairments in some patients present a challenge to obtaining informed consent for such trials. In addition, requiring written informed consent may select for patients who differ in clinically meaningful ways from patients who either are not able to provide it or who lack a surrogate who can do so for them. Most jurisdictions have mechanisms to allow, under certain circumstances, some types of clinical research without written informed consent. Some acute stroke trials are conducted with such waivers.
C1 [Karlawish, Jason] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kim, Scott Y. H.] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
RP Karlawish, J (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jason.karlawish@uphs.upenn.edu
NR 4
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD APR 19
PY 2016
VL 86
IS 16
BP 1472
EP 1473
DI 10.1212/WNL.0000000000002596
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DK4KS
UT WOS:000374887700007
PM 27009260
ER
PT J
AU Shi, YB
AF Shi, Yun-Bo
TI The 2015 Ming K Jeang Award for Excellence in Cell & Bioscience
SO CELL AND BIOSCIENCE
LA English
DT Review
AB Two research groups led by Dr. Bin Gao of National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, MD, USA and Dr. Keji Zhao of National Heart, Lung, and Blood Institute, National Institutes of Health, MD, USA, respectively, won the 2015 Ming K Jeang Award for excellence in Cell & Bioscience.
C1 [Shi, Yun-Bo] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD APR 19
PY 2016
VL 6
AR 27
DI 10.1186/s13578-016-0093-7
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ9UK
UT WOS:000374558200001
PM 27099702
ER
PT J
AU Lu, SY
Jang, H
Zhang, J
Nussinov, R
AF Lu, Shaoyong
Jang, Hyunbum
Zhang, Jian
Nussinov, Ruth
TI Inhibitors of Ras-SOS Interactions
SO CHEMMEDCHEM
LA English
DT Review
DE H-Ras; KRAS; K-Ras; oncogenic mutations; peptide mimetics;
protein-protein interactions
ID PROTEIN-PROTEIN INTERACTIONS; GUANINE-NUCLEOTIDE EXCHANGE;
SMALL-MOLECULE INHIBITORS; SMALL GTPASE K-RAS4B; CANCER-THERAPY;
HYPERVARIABLE REGION; SIGNAL-TRANSDUCTION; RATIONAL DESIGN;
ONCOPROTEIN-INHIBITORS; EFFECTOR INTERACTIONS
AB Activating Ras mutations are found in about 30% of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose pathway drug cocktails, that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal.
C1 [Lu, Shaoyong; Zhang, Jian] Shanghai Jiao Tong Univ, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Sch Med,Dept Pathophysiol, Shanghai 200025, Peoples R China.
[Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Sch Med,Dept Pathophysiol, Shanghai 200025, Peoples R China.; Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
EM jian.zhang@sjtu.edu.cn; NussinoR@helix.nih.gov
FU National Basic Research Program of China (973 Program) [2015CB910403];
National Natural Science Foundation of China [81322046, 81302698,
81473137]; Shanghai Rising-Star Program [13A1402300]; Program for New
Century Excellent Talents in University [NCET-12-0355]; Shanghai Health
and Family Planning Commission [20154Y0058]; Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health (NIH) [HHSN261200800001E]; Intramural Research Program of the
NIH, Frederick National Laboratory, Center for Cancer Research
FX This work was supported by the National Basic Research Program of China
(973 Program) (2015CB910403), the National Natural Science Foundation of
China (81322046, 81302698, 81473137), the Shanghai Rising-Star Program
(13A1402300) the Program for New Century Excellent Talents in University
(NCET-12-0355), and the Shanghai Health and Family Planning Commission
(20154Y0058). This project has been funded in whole or in part with
Federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health (NIH), under contract
HHSN261200800001E. This research was supported [ in part] by the
Intramural Research Program of the NIH, Frederick National Laboratory,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the US Department of Health
and Human Services, nor does the mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 80
TC 6
Z9 6
U1 9
U2 17
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD APR 19
PY 2016
VL 11
IS 8
SI SI
BP 814
EP 821
DI 10.1002/cmdc.201500481
PG 8
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK1SE
UT WOS:000374693500008
PM 26630662
ER
PT J
AU Sohn, M
Ivanova, P
Brown, HA
Toth, DJ
Varnai, P
Kim, YJ
Balla, T
AF Sohn, Mira
Ivanova, Pavlina
Brown, H. Alex
Toth, Daniel J.
Varnai, Peter
Kim, Yeun Ju
Balla, Tamas
TI Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol
4-phosphate metabolism at ER-PM and ER-Golgi junctions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE phosphatidylserine; phosphatidylinositol; PI 4-kinase; ER-PM junctions;
lipid transfer
ID PHOSPHOINOSITIDE PHOSPHATASE; TRANSFER PROTEINS; LIPID-TRANSFER;
PHOSPHATIDYLSERINE; POOLS; MULTIPLE; REVEALS; CELLS; SAC1; TRAFFICKING
AB Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in the PTDSS1 gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.
C1 [Sohn, Mira; Toth, Daniel J.; Kim, Yeun Ju; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Ivanova, Pavlina; Brown, H. Alex] Vanderbilt Univ, Dept Pharmacol & Biochem, Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Sch Med, Nashville, TN 37232 USA.
[Varnai, Peter] Semmelweis Univ, Sch Med, Dept Physiol, H-1094 Budapest, Hungary.
RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
OI Toth, Daniel/0000-0001-6670-3348; Balla, Tamas/0000-0002-9077-3335
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development at the National Institutes of Health; Bixler Johnson Mayes
Endowed Chair; Vanderbilt Institute of Chemical Biology; National
Research, Development, and Innovation Fund [NKFI K105006]
FX This work was supported in part by the intramural research program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development at the National Institutes of Health. The work from the
H.A.B. laboratory was supported partly by the Bixler Johnson Mayes
Endowed Chair and the Vanderbilt Institute of Chemical Biology. P.V. was
supported by the National Research, Development, and Innovation Fund
(Grant NKFI K105006).
NR 31
TC 3
Z9 3
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 19
PY 2016
VL 113
IS 16
BP 4314
EP 4319
DI 10.1073/pnas.1525719113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7LV
UT WOS:000374393800038
PM 27044099
ER
PT J
AU Fu, Y
Winter, PW
Rojas, R
Wang, V
McAuliffe, M
Patterson, GH
AF Fu, Yan
Winter, Peter W.
Rojas, Raul
Wang, Victor
McAuliffe, Matthew
Patterson, George H.
TI Axial superresolution via multiangle TIRF microscopy with sequential
imaging and photobleaching
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE total internal reflection fluorescence; axial superresolution;
photobleaching
ID INTERNAL-REFLECTION FLUORESCENCE; OPTICAL RECONSTRUCTION MICROSCOPY;
DIFFRACTION-LIMIT; RESOLUTION; NANOSCALE; CELLS; DYNAMICS; (IM)-M-5;
SAMPLES; STORM
AB We report superresolution optical sectioning using a multiangle total internal reflection fluorescence (TIRF) microscope. TIRF images were constructed from several layers within a normal TIRF excitation zone by sequentially imaging and photobleaching the fluorescent molecules. The depth of the evanescent wave at different layers was altered by tuning the excitation light incident angle. The angle was tuned from the highest (the smallest TIRF depth) toward the critical angle (the largest TIRF depth) to preferentially photobleach fluorescence from the lower layers and allow straightforward observation of deeper structures withoutmasking by the brighter signals closer to the coverglass. Reconstruction of the TIRF images enabled 3D imaging of biological samples with 20-nm axial resolution. Two-color imaging of epidermal growth factor (EGF) ligand and clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis during internalization. Furthermore, Bayesian analysis of images collected during the photobleaching step of each plane enabled lateral super-resolution (<100 nm) within each of the sections.
C1 [Fu, Yan; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA.
[Winter, Peter W.] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA.
[Rojas, Raul] Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
[Wang, Victor; McAuliffe, Matthew] NIH, Biomed Imaging Res Serv Sect, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA.
EM pattersg@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Biomedical Imaging and Bioengineering
FX We thank Hari Shroff for helpful discussions and a critical reading of
the manuscript. This work was supported by the Intramural Research
Program of the National Institutes of Health, including the National
Institute of Biomedical Imaging and Bioengineering. This study was
performed using the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health
(https://hpc.nih.gov).
NR 35
TC 2
Z9 2
U1 9
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 19
PY 2016
VL 113
IS 16
BP 4368
EP 4373
DI 10.1073/pnas.1516715113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7LV
UT WOS:000374393800047
PM 27044072
ER
PT J
AU Zeitlin, L
Geisbert, JB
Deer, DJ
Fenton, KA
Bohorov, O
Bohorova, N
Goodman, C
Kim, D
Hiatt, A
Pauly, MH
Velasco, J
Whaley, KJ
Altmann, F
Gruber, C
Steinkellner, H
Honko, AN
Kuehne, AI
Aman, MJ
Sahandi, S
Enterlein, S
Zhan, XG
Enria, D
Geisbert, TW
AF Zeitlin, Larry
Geisbert, Joan B.
Deer, Daniel J.
Fenton, Karla A.
Bohorov, Ognian
Bohorova, Natasha
Goodman, Charles
Kim, Do
Hiatt, Andrew
Pauly, Michael H.
Velasco, Jesus
Whaley, Kevin J.
Altmann, Friedrich
Gruber, Clemens
Steinkellner, Herta
Honko, Anna N.
Kuehne, Ana I.
Aman, M. Javad
Sahandi, Sara
Enterlein, Sven
Zhan, Xiaoguo
Enria, Delia
Geisbert, Thomas W.
TI Monoclonal antibody therapy for Junin virus infection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Junin; therapy; immunotherapy; hemorrhagic fever
ID ARGENTINE HEMORRHAGIC-FEVER; GUINEA-PIGS; IMMUNE PLASMA; EFFICACY;
DISEASE; IGG; ENCEPHALITIS; PATHOGENESIS; EXPRESSION; MODEL
AB Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them(J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic.
C1 [Zeitlin, Larry; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Hiatt, Andrew; Pauly, Michael H.; Velasco, Jesus; Whaley, Kevin J.] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.
[Geisbert, Joan B.; Deer, Daniel J.; Fenton, Karla A.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Geisbert, Joan B.; Deer, Daniel J.; Fenton, Karla A.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Altmann, Friedrich; Gruber, Clemens] Univ Nat Resources & Appl Life Sci, Dept Chem, A-1190 Vienna, Austria.
[Steinkellner, Herta] Univ Nat Resources & Appl Life Sci, Dept Appl Genet & Cell Biol, A-1190 Vienna, Austria.
[Honko, Anna N.; Kuehne, Ana I.] US Army Med Res Inst Infect Dis, Virol Div, Frederick, MD 21702 USA.
[Aman, M. Javad; Sahandi, Sara; Enterlein, Sven; Zhan, Xiaoguo] Integrated BioTherapeut Inc, Gaithersburg, MD 20878 USA.
[Enria, Delia] Inst Nacl Enfermedades Virales Humanas, Buenos Aires, DF, Argentina.
[Honko, Anna N.] NIAID, Integrated Res Facil, Frederick, MD 21702 USA.
RP Zeitlin, L (reprint author), Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.; Geisbert, TW (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.; Geisbert, TW (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
EM larry.zeitlin@mappbio.com; twgeisbe@UTMB.EDU
RI Steinkellner, Herta/N-4267-2016;
OI Steinkellner, Herta/0000-0003-4823-1505; Honko, Anna/0000-0001-9165-148X
FU National Institute of Allergy and Infectious Disease [AI111391]
FX We thank Drs. Yuri Gleba and Victor Klimyuk (Icon Genetics) for access
to the magnICON expression technology and Natalie Dobias and the
Research Histopathology Core at UTMB for optimization of the
immunohistochemistry protocol. This publication was made possible by
National Institute of Allergy and Infectious Disease Grant AI111391.
NR 33
TC 4
Z9 5
U1 2
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 19
PY 2016
VL 113
IS 16
BP 4458
EP 4463
DI 10.1073/pnas.1600996113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7LV
UT WOS:000374393800062
PM 27044104
ER
PT J
AU Chang, C
Leopold, DA
Scholvinck, ML
Mandelkow, H
Picchioni, D
Liu, X
Ye, FQ
Turchi, JN
Duyn, JH
AF Chang, Catie
Leopold, David A.
Schoelvinck, Marieke Louise
Mandelkow, Hendrik
Picchioni, Dante
Liu, Xiao
Ye, Frank Q.
Turchi, Janita N.
Duyn, Jeff H.
TI Tracking brain arousal fluctuations with fMRI
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE resting-state fMRI; spontaneous fluctuations; arousal; electrophysiology
ID RESTING-STATE FMRI; DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY;
ALPHA-RHYTHM; SIMULTANEOUS EEG; SLEEP; SIGNAL; WAKEFULNESS; VIGILANCE;
CORTEX
AB Changes in brain activity accompanying shifts in vigilance and arousal can interfere with the study of other intrinsic and task-evoked characteristics of brain function. However, the difficulty of tracking and modeling the arousal state during functional MRI (fMRI) typically precludes the assessment of arousal-dependent influences on fMRI signals. Here we combine fMRI, electrophysiology, and the monitoring of eyelid behavior to demonstrate an approach for tracking continuous variations in arousal level from fMRI data. We first characterize the spatial distribution of fMRI signal fluctuations that track a measure of behavioral arousal; taking this pattern as a template, and using the local field potential as a simultaneous and independent measure of cortical activity, we observe that the time-varying expression level of this template in fMRI data provides a close approximation of electrophysiological arousal. We discuss the potential benefit of these findings for increasing the sensitivity of fMRI as a cognitive and clinical biomarker.
C1 [Chang, Catie; Mandelkow, Hendrik; Picchioni, Dante; Liu, Xiao; Duyn, Jeff H.] NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Leopold, David A.; Ye, Frank Q.] NIMH, Neurophysiol Imaging Facil, NINDS, NIH, Bethesda, MD 20892 USA.
[Leopold, David A.; Ye, Frank Q.] NEI, NIH, Bethesda, MD 20892 USA.
[Schoelvinck, Marieke Louise] Max Planck Gesell, Ernst Strungmann Inst Neurosci Cooperat, D-60528 Frankfurt, Germany.
[Turchi, Janita N.] NIMH, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA.
RP Chang, C (reprint author), NINDS, Adv Magnet Resonance Imaging Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM catie.chang@nih.gov
RI Liu, Xiao/C-5943-2016;
OI Leopold, David/0000-0002-1345-6360
FU Intramural Research Programs of the National Institute of Neurological
Disorders and Stroke; National Institute of Mental Health, National
Institutes of Health
FX We thank Brian Russ, Mikail Rubinov, Jennifer Evans, and Michael Chen
for valuable discussions and David Yu and Katy Smith for assistance with
experiments. This research was supported in part by the Intramural
Research Programs of the National Institute of Neurological Disorders
and Stroke and the National Institute of Mental Health, National
Institutes of Health.
NR 70
TC 2
Z9 2
U1 6
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 19
PY 2016
VL 113
IS 16
BP 4518
EP 4523
DI 10.1073/pnas.1520613113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7LV
UT WOS:000374393800072
PM 27051064
ER
PT J
AU Brauner, EV
Andersen, ZJ
Frederiksen, M
Specht, IO
Hougaard, KS
Ebbehoj, N
Bailey, J
Giwercman, A
Steenland, K
Longnecker, MP
Bonde, JP
AF Brauner, Elvira Vaclavik
Andersen, Zorana Jovanovic
Frederiksen, Marie
Specht, Ina Olmer
Hougaard, Karin Sorig
Ebbehoj, Niels
Bailey, Janice
Giwercman, Aleksander
Steenland, Kyle
Longnecker, Matthew Paul
Bonde, Jens Peter
TI Health Effects of PCBs in Residences and Schools (HESPERUS): PCB -
health Cohort Profile
SO SCIENTIFIC REPORTS
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS PCB; NATIONAL DIABETES REGISTER; INDOOR AIR;
CONTAMINATED SCHOOL; EXPOSURE; INHALATION; TEACHERS; BUILDINGS; WORKING
AB Polychlorinated-biphenyls (PCBs) were introduced in the late 1920s and used until the 1970s when they were banned in most countries due to evidence of environmental build-up and possible adverse health effects. However they still persist in the environment, indoors and in humans. Indoor air in contaminated buildings may confer airborne exposure markedly above background regional PCB levels. To date, no epidemiological studies have assessed the health effects from exposure to semi-volatile PCBs in the indoor environment. Indoor air PCBs are generally less chlorinated than PCBs that are absorbed via the diet, or via past occupational exposure; therefore their health effects require separate risk assessment. Two separate cohorts of individuals who have either attended schools (n = 66,769; 26% exposed) or lived in apartment buildings (n = 37,185; 19% exposed), where indoor air PCB concentrations have been measured were created. An individual estimate of long-term airborne PCB exposure was assigned based on measurements. The cohorts will be linked to eight different national data sources on mortality, school records, residential history, socioeconomic status, and chronic disease and reproductive outcomes. The linking of indoor air exposures with health outcomes provides a dataset unprecedented worldwide. We describe a project, called HESPERUS (Health Effects of PCBs in Residences and Schools), which will be the first study of the long term health effects of the lower-chlorinated, semi-volatile PCBs in the indoor environment.
C1 [Brauner, Elvira Vaclavik] Univ Copenhagen, Rigshosp Glostrup, Capital Reg Denmark, Res Ctr Prevent & Hlth,Ctr Hlth, Copenhagen, Denmark.
[Brauner, Elvira Vaclavik; Specht, Ina Olmer; Ebbehoj, Niels; Bonde, Jens Peter] Univ Copenhagen, Inst Publ Hlth, Bispebjerg Frederiksberg Hosp, Dept Occupat & Environm Med, Copenhagen, Denmark.
[Andersen, Zorana Jovanovic] Univ Copenhagen, Fac Hlth Sci, Ctr Epidemiol & Screening, Dept Publ Hlth, Copenhagen, Denmark.
[Frederiksen, Marie] Aalborg Univ, Danish Bldg Res Inst, Dept Energy Environm & Indoor Climate, Aalborg, Denmark.
[Hougaard, Karin Sorig] Natl Res Ctr Working Environm, Copenhagen, Denmark.
[Bailey, Janice] Univ Laval, Dept Anim Sci, Ctr Rech Biol Reprod, Quebec City, PQ G1K 7P4, Canada.
[Giwercman, Aleksander] Lund Univ, Dept Translat Med, Mol Reprod Med, S-22100 Lund, Sweden.
[Steenland, Kyle] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA.
[Longnecker, Matthew Paul] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Brauner, EV (reprint author), Univ Copenhagen, Rigshosp Glostrup, Capital Reg Denmark, Res Ctr Prevent & Hlth,Ctr Hlth, Copenhagen, Denmark.; Brauner, EV (reprint author), Univ Copenhagen, Inst Publ Hlth, Bispebjerg Frederiksberg Hosp, Dept Occupat & Environm Med, Copenhagen, Denmark.
EM elvira.vaclavik.braeuner@regionh.dk
OI Hougaard, Karin/0000-0002-3386-0512; Longnecker,
Matthew/0000-0001-6073-5322; Specht, Ina Olmer/0000-0002-3114-4715
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences; National Institutes
of Health applications from the Capital region of Denmark
FX We thank Harald Meyer, Thomas Hougaard and Lars Gunnarsen for valuable
discussions. This work was supported in part by the Intramural Research
Program of the National Institutes of Health, National Institute of
Environmental Health Sciences and in part by a starting grant for
National Institutes of Health applications from the Capital region of
Denmark.
NR 35
TC 1
Z9 1
U1 12
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 19
PY 2016
VL 6
AR 24571
DI 10.1038/srep24571
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7GM
UT WOS:000374379900001
PM 27090775
ER
PT J
AU Jee, YH
Lebenthal, Y
Chaemsaithong, P
Yan, G
Peran, I
Wellstein, A
Romero, R
Baron, J
AF Jee, Youn Hee
Lebenthal, Yael
Chaemsaithong, Piya
Yan, Gai
Peran, Ivana
Wellstein, Anton
Romero, Roberto
Baron, Jeffrey
TI Midkine and Pleiotrophin Concentrations in Amniotic Fluid in Healthy and
Complicated Pregnancies
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR PLEIOTROPHIN; ACID-RESPONSIVE GENE; ENDOGENOUS RETROVIRUS;
MOUSE EMBRYOGENESIS; DIFFERENTIATION FACTOR; PRETERM DELIVERY;
ADULT-RAT; EXPRESSION; MK; FETAL
AB Background
Midkine (MDK) and pleiotrophin (PTN) are heparin-binding growth factors that, in rodents, are highly expressed in early life and decrease to undetectable levels by adulthood. The potential roles of MDK and PTN in human growth and development are not completely elucidated.
Method and Findings
To delineate the role of MDK and PTN in human development, we developed high sensitivity assays to measure their concentrations in amniotic fluid (AF) at various gestational ages in both healthy and complicated pregnancies. We found that both of these growth factors could be readily measured in AF and that the concentrations were higher than most cytokines previously reported in AF.
Conclusion
The concentration of MDK but not that of PTN declined with gestational age. Both MDK and PTN concentrations were found to be lower in pregnancies that were complicated by chorioamnionitis at term, raising the possibility that these growth factors might be useful as markers for infection.
C1 [Jee, Youn Hee; Lebenthal, Yael; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Lebenthal, Yael] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Chaemsaithong, Piya; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res, Detroit, MI USA.
[Yan, Gai; Peran, Ivana; Wellstein, Anton] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Yan, Gai; Peran, Ivana; Wellstein, Anton] Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Baron, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM jeffrey.baron@nih.gov
FU Thrasher Research Fund; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD)
FX This work was supported by a grant from the Thrasher Research Fund and
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
[https://www.thrasherresearch.org/default.aspx].
NR 39
TC 1
Z9 1
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 18
PY 2016
VL 11
IS 4
AR e0153325
DI 10.1371/journal.pone.0153325
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ9IK
UT WOS:000374527000017
PM 27089523
ER
PT J
AU Rast, TJ
Kullas, AL
Southern, PJ
Davis, DA
AF Rast, Timothy J.
Kullas, Amy L.
Southern, Peter J.
Davis, Dana A.
TI Human Epithelial Cells Discriminate between Commensal and Pathogenic
Interactions with Candida albicans
SO PLOS ONE
LA English
DT Article
ID TOLL-LIKE RECEPTORS; ENDOTHELIAL-CELLS; PATHWAY; INFECTIONS; ADHERENCE;
PROMOTER; BINDING; GENES; SHOCK; LINE
AB The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.
C1 [Rast, Timothy J.; Kullas, Amy L.; Southern, Peter J.; Davis, Dana A.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
[Rast, Timothy J.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ USA.
[Kullas, Amy L.] NIH, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA.
RP Davis, DA (reprint author), Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
EM dadavis@umn.edu
FU University of Minnesota [18805]; National Institutes of Health [1R01
AI064054-01]; Burroughs Wellcome Fund [1004419]
FX Funded by University of Minnesota (http://www.research.umn.edu): #18805,
National Institutes of Health
(http://www.niaid.nih.gov/Pages/default.aspx): 1R01 AI064054-01, and
Burroughs Wellcome Fund (http://www.bwfund.org): #1004419. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 33
TC 1
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 18
PY 2016
VL 11
IS 4
AR e0153165
DI 10.1371/journal.pone.0153165
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ9IK
UT WOS:000374527000011
PM 27088599
ER
PT J
AU Chaiworapongsa, T
Romero, R
Whitten, AE
Korzeniewski, SJ
Chaemsaithong, P
Hernandez-Andrade, E
Yeo, L
Hassan, SS
AF Chaiworapongsa, Tinnakorn
Romero, Roberto
Whitten, Amy E.
Korzeniewski, Steven J.
Chaemsaithong, Piya
Hernandez-Andrade, Edgar
Yeo, Lami
Hassan, Sonia S.
TI The use of angiogenic biomarkers in maternal blood to identify which SGA
fetuses will require a preterm delivery and mothers who will develop
pre-eclampsia
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Angiogenic; Anti-angiogenic factors; intrauterine growth restriction
(IUGR); placental growth factor; pregnancy; soluble endoglin; sflt-1;
soluble vascular endothelial growth factor receptor-1; umbilical artery
Doppler; uterine artery Doppler
ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH RESTRICTION; UTERINE ARTERY
DOPPLER; FUNDAL HEIGHT-MEASUREMENT; LATE-ONSET PREECLAMPSIA; LOW-RISK
POPULATION; FACTOR RECEPTOR-1 CONCENTRATION; RANDOMIZED
CONTROLLED-TRIAL; TYROSINE KINASE-1 SFLT-1; NORMAL FETAL GROWTH
AB Objective: To determine (1) whether maternal plasma concentrations of angiogenic and anti-angiogenic factors can predict which mothers diagnosed with suspected small for gestational age fetuses (sSGA) will develop pre-eclampsia (PE) or require an indicated early preterm delivery (34 weeks of gestation); and (2) whether risk assessment performance is improved using these proteins in addition to clinical factors and Doppler parameters.Methods: This prospective cohort study included women with singleton pregnancies diagnosed with sSGA (estimated fetal weight <10th percentile) between 24 and 34 weeks of gestation (n=314). Plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin (sEng) and placental growth factor (PlGF) were determined in maternal blood obtained at the time of diagnosis. Doppler velocimetry of the umbilical (Umb) and uterine (UT) arteries was performed. The outcomes were (1) subsequent development of PE; and (2) indicated preterm delivery at 34 weeks of gestation (excluding deliveries as a result of spontaneous preterm labor, preterm pre-labor rupture of membranes or chorioamnionitis).Results: (1) The prevalence of PE and indicated preterm delivery was 9.2% (n=29/314) and 7.3% (n=23/314), respectively; (2) the area under the receiver operating characteristic curve (AUC) for the identification of patients who developed PE and/or required indicated preterm delivery was greater than 80% for the UT artery pulsatility index (PI) z-score and each biochemical marker (including their ratios) except sVEGFR-1 MoM; (3) using cutoffs at a false positive rate of 15%, women with abnormal plasma concentrations of angiogenic/anti-angiogenic factors were 7-13 times more likely to develop PE, and 12-22 times more likely to require preterm delivery than those with normal plasma MoM concentrations of these factors; (4) sEng, PlGF, PIGF/sEng and PIGF/sVEGFR-1 ratios MoM, each contributed significant information about the risk of PE beyond that provided by clinical factors and/or Doppler parameters: women who had low MoM values for these biomarkers were at 5-9 times greater risk of developing PE than women who had normal values, adjusting for clinical factors and Doppler parameters (adjusted odds ratio for PlGF: 9.1, PlGF/sEng: 5.6); (5) the concentrations of sVEGFR-1 and PlGF/sVEGFR-1 ratio MoM, each contributed significant information about the risk of indicated preterm delivery beyond that provided by clinical factors and/or Doppler parameters: women who had abnormal values were at 8-9 times greater risk for indicated preterm delivery, adjusting for clinical factors and Doppler parameters; and (6) for a two-stage risk assessment (Umb artery Doppler followed by Ut artery Doppler plus biochemical markers), among women who had normal Umb artery Doppler velocimetry (n=279), 21 (7.5%) developed PE and 11 (52%) of these women were identified by an abnormal UT artery Doppler mean PI z-score (>2SD): a combination of PlGF/sEng ratio MoM concentration and abnormal UT artery Doppler velocimetry increased the sensitivity of abnormal UT artery Doppler velocimetry to 76% (16/21) at a fixed false-positive rate of 10% (p=0.06).Conclusion: Angiogenic and anti-angiogenic factors measured in maternal blood between 24 and 34 weeks of gestation can identify the majority of mothers diagnosed with suspected SGA who subsequently developed PE or those who later required preterm delivery 34 weeks of gestation.
Moreover, incorporation of these biochemical markers significantly improves risk assessment performance for these outcomes beyond that of clinical factors and uterine and umbilical artery Doppler velocimetry.
C1 [Chaiworapongsa, Tinnakorn; Romero, Roberto; Whitten, Amy E.; Korzeniewski, Steven J.; Chaemsaithong, Piya; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto; Whitten, Amy E.; Korzeniewski, Steven J.; Chaemsaithong, Piya; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Whitten, Amy E.; Korzeniewski, Steven J.; Chaemsaithong, Piya; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Dept Mol Obstet & Genet, Detroit, MI USA.
RP Chaiworapongsa, T; Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM tchaiwor@med.wayne.edu; romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX The authors report no conflicts of interest. This research was
supported, in part, by the Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, DHHS.
NR 203
TC 3
Z9 3
U1 2
U2 11
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD APR 17
PY 2016
VL 29
IS 8
BP 1214
EP 1228
DI 10.3109/14767058.2015.1048431
PG 15
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DB7TJ
UT WOS:000368718700005
PM 26303962
ER
PT J
AU Glas, GJ
Neto, AS
Horn, J
Cochran, A
Dixon, B
Elamin, EM
Faraklas, I
Dissanaike, S
Miller, AC
Schultz, MJ
AF Glas, Gerie J.
Neto, Ary Serpa
Horn, Janneke
Cochran, Amalia
Dixon, Barry
Elamin, Elamin M.
Faraklas, Iris
Dissanaike, Sharmila
Miller, Andrew C.
Schultz, Marcus J.
TI Nebulized heparin for patients under mechanical ventilation: an
individual patient data meta-analysis
SO ANNALS OF INTENSIVE CARE
LA English
DT Article
DE Anticoagulants; Administration; Inhalation; Mechanical ventilation;
Humans; Heparin; Intensive care
ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED
CONTROLLED-TRIAL; ACTIVATED PROTEIN-C; SEVERE SEPSIS; INHALATION INJURY;
ANTICOAGULANT-THERAPY; FIBRIN DEPOSITION; ANTITHROMBIN-III;
N-ACETYLCYSTEINE
AB Pulmonary coagulopathy is a characteristic feature of lung injury including ventilator-induced lung injury. The aim of this individual patient data meta-analysis is to assess the effects of nebulized anticoagulants on outcome of ventilated intensive care unit (ICU) patients. A systematic search of PubMed (1966-2014), Scopus, EMBASE, and Web of Science was conducted to identify relevant publications. Studies evaluating nebulization of anticoagulants in ventilated patients were screened for inclusion, and corresponding authors of included studies were contacted to provide individual patient data. The primary endpoint was the number of ventilator-free days and alive at day 28. Secondary endpoints included hospital mortality, ICU- and hospital-free days at day 28, and lung injury scores at day seven. We constructed a propensity score-matched cohort for comparisons between patients treated with nebulized anticoagulants and controls. Data from five studies (one randomized controlled trial, one open label study, and three studies using historical controls) were included in the meta-analysis, compassing 286 patients. In all studies unfractionated heparin was used as anticoagulant. The number of ventilator-free days and alive at day 28 was higher in patients treated with nebulized heparin compared to patients in the control group (14 [IQR 0-23] vs. 6 [IQR 0-22]), though the difference did not reach statistical significance (P = 0.459). The number of ICU-free days and alive at day 28 was significantly higher, and the lung injury scores at day seven were significantly lower in patients treated with nebulized heparin. In the propensity score-matched analysis, there were no differences in any of the endpoints. This individual patient data meta-analysis provides no convincing evidence for benefit of heparin nebulization in intubated and ventilated ICU patients. The small patient numbers and methodological shortcomings of included studies underline the need for high-quality well-powered randomized controlled trials.
C1 [Glas, Gerie J.; Horn, Janneke; Schultz, Marcus J.] Univ Amsterdam, Acad Med Ctr, Dept Intens Care, Lab Expt Intens Care & Anesthesiol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Neto, Ary Serpa] Hosp Israelita Albert Einstein, Dept Crit Care Med, Sao Paulo, Brazil.
[Neto, Ary Serpa] ABC, Fac Med, Dept Crit Care Med, Santo Andre, Brazil.
[Neto, Ary Serpa] ABC, Fac Med, Program Postgrad Res & Innovat, Santo Andre, Brazil.
[Cochran, Amalia; Faraklas, Iris] Univ Utah, Hlth Sci Ctr, Dept Surg, Salt Lake City, UT USA.
[Dixon, Barry] St Vincents Hosp, Dept Intens Care, Melbourne, Vic, Australia.
[Elamin, Elamin M.] Univ S Florida, Dept Internal Med, James A Haley Vet Hosp, Div Pulm Crit Care & Sleep Med, Tampa, FL 33612 USA.
[Dissanaike, Sharmila] Texas Tech Univ, Hlth Sci Ctr, Dept Surg, Lubbock, TX 79430 USA.
[Miller, Andrew C.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Miller, Andrew C.] W Virginia Univ, Dept Emergency Med, Morgantown, WV 26506 USA.
RP Glas, GJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Intens Care, Lab Expt Intens Care & Anesthesiol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM g.j.glas@amc.uva.nl
RI Serpa Neto, Ary/D-1927-2012;
OI Serpa Neto, Ary/0000-0003-1520-9387; Miller, Andrew/0000-0001-8474-5090
FU 'de Nederlandse Brandwondenstichting' (the Dutch Burn Association,
Beverwijk, the Netherlands)
FX This study was funded by 'de Nederlandse Brandwondenstichting' (the
Dutch Burn Association, Beverwijk, the Netherlands).
NR 69
TC 0
Z9 0
U1 2
U2 51
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 2110-5820
J9 ANN INTENSIVE CARE
JI Ann. Intensive Care
PD APR 16
PY 2016
VL 6
AR 33
DI 10.1186/s13613-016-0138-4
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA DN7ZJ
UT WOS:000377298400001
PM 27083915
ER
PT J
AU Forlino, A
Marini, JC
AF Forlino, Antonella
Marini, Joan C.
TI Osteogenesis imperfecta
SO LANCET
LA English
DT Review
ID EHLERS-DANLOS-SYNDROME; EPITHELIUM-DERIVED FACTOR; CIS-TRANS-ISOMERASE;
PROLYL 3-HYDROXYLATION COMPLEX; CARTILAGE-ASSOCIATED PROTEIN;
PROCOLLAGEN C-PROTEINASE; COLLAGEN TRIPLE-HELIX; BRITTLE BONE-DISEASE; I
PROCOLLAGEN; CYCLOPHILIN-B
AB Osteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post-translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation.
C1 [Forlino, Antonella] Univ Pavia, Dept Mol Med, Biochem Unit, Via Palestro 3, I-27100 Pavia, Italy.
[Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20855 USA.
RP Marini, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20855 USA.
EM oidoc@helix.nih.gov
FU NICHD; Fondazione Cariplo [2013-0612]; Telethon [GGP13098]
FX The authors thank the members of the Marini Laboratory for critical
review of the manuscript, especially Wayne A Cabral and Aileen M Barnes
for feedback on figures. Figures were prepared by Jeremy Swan and Erin
Fincher of The Unit on Computer Support Services, Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD). When
writing this Seminar, JCM was supported by intramural funding from the
NICHD and AF was supported by the Fondazione Cariplo grant n. 2013-0612
and Telethon grant n. GGP13098. The funders did not have any role in
study design, the collection, analysis, and interpretation of data, the
writing of the Seminar, or the decision to submit the Seminar for
publication.
NR 139
TC 45
Z9 45
U1 20
U2 36
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD APR 16
PY 2016
VL 387
IS 10028
BP 1657
EP 1671
DI 10.1016/S0140-6736(15)00728-X
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ3ZL
UT WOS:000374145100033
PM 26542481
ER
PT J
AU Stumpo, DJ
Trempus, CS
Tucker, CJ
Huang, WC
Li, LP
Kluckman, K
Bortner, DM
Blackshear, PJ
AF Stumpo, Deborah J.
Trempus, Carol S.
Tucker, Charles J.
Huang, Weichun
Li, Leping
Kluckman, Kimberly
Bortner, Donna M.
Blackshear, Perry J.
TI Deficiency of the placenta- and yolk sac-specific tristetraprolin family
member ZFP36L3 identifies likely mRNA targets and an unexpected link to
placental iron metabolism
SO DEVELOPMENT
LA English
DT Article
DE Deadenylation; mRNA binding proteins; mRNA decay; Placenta; Zinc finger
proteins
ID ZINC-FINGER PROTEINS; GROWTH-FACTOR; ENDOTHELIAL LIPASE; FACTOR-ALPHA;
EXPRESSION; BINDING; GENE; DEADENYLATION; EGF; DYSREGULATION
AB The ZFP36L3 protein is a rodent-specific, placenta- and yolk sacspecific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. We addressed the hypotheses that the absence of ZFP36L3 would result in the accumulation of target transcripts in placenta and/or yolk sac, and that some of these would be important for female reproductive physiology and overall fecundity. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. We found Zfp36l3 to be paternally imprinted, with profound parent-of-origin effects on gene expression. The protein was highly expressed in the syncytiotrophoblast cells of the labyrinth layer of the placenta, and the epithelial cells of the yolk sac. RNA-Seq of placental mRNA from Zfp36l3 knockout (KO) mice revealed many significantly upregulated transcripts, whereas there were few changes in KO yolk sacs. Many of the upregulated placental transcripts exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. Several dozen transcripts were deemed high probability targets of ZFP36L3; these include proteins known to be involved in trophoblast and placenta physiology. Type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability in KO stem cells. This receptor is crucial for placental iron uptake, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life.
C1 [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
[Trempus, Carol S.] NIEHS, Lab Clin Res, POB 12233, Res Triangle Pk, NC 27709 USA.
[Tucker, Charles J.] NIEHS, Confocal Microscopy Core, POB 12233, Res Triangle Pk, NC 27709 USA.
[Huang, Weichun; Li, Leping] NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
[Kluckman, Kimberly; Bortner, Donna M.] TransViragen Inc, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
EM black009@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences. Deposited in PMC for release after 12 months.
NR 39
TC 1
Z9 1
U1 1
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD APR 15
PY 2016
VL 143
IS 8
BP 1424
EP 1433
DI 10.1242/dev.130369
PG 10
WC Developmental Biology
SC Developmental Biology
GA DY6TN
UT WOS:000385261300019
PM 26952984
ER
PT J
AU Maggio, R
Fasciani, I
Rossi, M
Di Gregorio, J
Pietrantoni, I
Puca, V
Flati, V
Scarselli, M
AF Maggio, Roberto
Fasciani, Irene
Rossi, Mario
Di Gregorio, Jacopo
Pietrantoni, Ilaria
Puca, Valentina
Flati, Vincenzo
Scarselli, Marco
TI Variants of G protein-coupled receptors: a reappraisal of their role in
receptor regulation
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE dimerization; G protein-coupled receptor; internal ribosome entry site;
muscarinic receptor; receptor fragment; slice variant
ID MESSENGER-RNA; DOPAMINE-RECEPTORS; SPLICE VARIANT; DIMERIZATION;
TRAFFICKING; MUTANT; OLIGOMERIZATION; RECONSTITUTION; PHARMACOLOGY;
COEXPRESSION
AB Truncated or shorter forms of G protein-coupled receptors (GPCRs), originating by alternative splicing, have been considered physiologically irrelevant for a rather long time. Nevertheless, it is now recognized that alternative splicing variants of GPCRs greatly increase the total number of receptor isoforms and can regulate receptor trafficking and signalling. Furthermore, dimerization of these truncated variants with other receptors concurs to expand receptor diversity. Highly truncated variants of GPCRs, typically, are retained in the endoplasmic reticulum (ER) and by heteromerization prevent the wild-type receptor to reach the plasma membrane, exerting a dominant-negative effect on its function. This can be responsible for some pathological conditions but in some other cases, it can offer protection from a disease because the expression of the receptor, that is necessary for binding an infectious agent, is attenuated. Here, we propose a possible new mechanism of creation of truncated GPCR variants through an internal ribosome entry site (IRES), a nucleotide sequence that allows cap independent translation of proteins by recruiting the ribosome in proximity of an internal initiation codon. We suggest that an IRES, situated in the third cytoplasmic loop, could be responsible for the translation of the last two transmembrane (TM) regions of the muscarinic M-2 receptor. IRES driven expression of this C-terminal part of the muscarinic M-2 receptor could represent a novel and additional mechanism of receptor regulation.
C1 [Maggio, Roberto; Fasciani, Irene; Di Gregorio, Jacopo; Pietrantoni, Ilaria; Puca, Valentina; Flati, Vincenzo] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy.
[Rossi, Mario] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
[Scarselli, Marco] Univ Pisa, Dept Translat Res & New Technol Med & Surg, I-56126 Pisa, Italy.
RP Maggio, R (reprint author), Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy.
EM roberto.maggio@univaq.it
NR 42
TC 0
Z9 0
U1 1
U2 1
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0300-5127
EI 1470-8752
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD APR 15
PY 2016
VL 44
BP 589
EP 594
DI 10.1042/BST20150239
PN 2
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO1DF
UT WOS:000377518000039
PM 27068974
ER
PT J
AU Casado-Anguera, V
Bonaventura, J
Moreno, E
Navarro, G
Cortes, A
Ferre, S
Casado, V
AF Casado-Anguera, Veronica
Bonaventura, Jordi
Moreno, Estefania
Navarro, Gemma
Cortes, Antoni
Ferre, Sergi
Casado, Vicent
TI Evidence for the heterotetrameric structure of the adenosine
A(2A)-dopamine D-2 receptor complex
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE adenosine receptors; allosteric modulation; dopamine receptors;
G-protein-coupled receptor (GPCR); heteromerization; homodimerization
ID PROTEIN-COUPLED RECEPTOR; TARGET RESIDENCE TIME; A(2A) RECEPTOR;
DOPAMINE-D-2 RECEPTORS; FUNCTIONAL SELECTIVITY; PARKINSONS-DISEASE;
L-DOPA; ALLOSTERIC MODULATION; DRUG DEVELOPMENT; HETEROMERS
AB Heteromers of G-protein-coupled receptors (GPCRs) have emerged as potential novel targets for drug development. Accumulating evidence indicates that GPCRs can form homodimers and heteromers, with homodimers being the predominant species and oligomeric receptors being formed as multiples of dimers. Recently, heterotetrameric structures have been proposed for dopamine D-1 receptor (D1R)-dopamine D-3 receptor (D3R) and adenosine A(2A) receptor (A(2A)R)-dopamine D-2 receptor (D2R) heteromers. The structural model proposed for these complexes is a heteromer constituted by two receptor homodimers. The existence of GPCR homodimers and heteromers provides a structural basis for inter-protomer allosteric mechanisms that might account for a multiplicity of unique pharmacological properties. In this review, we focus on the A(2A)R-D2R heterotetramer as an example of an oligomeric structure that is key in the modulation of striatal neuronal function. We also review the interfaces involved in this and other recently reported heteromers of GPCRs. Furthermore, we discuss several published studies showing the ex vivo expression of A(2A)R-D2R heteromers. The ability of A(2A)R agonists to decrease the affinity of D2R agonists has been reported and, on the basis of this interaction, A(2A)R antagonists have been proposed as potential drugs for the treatment of Parkinson's disease. The heterotetrameric structure of the A(2A)R-D2R complex offers a novel model that can provide new clues about how to adjust the drug dosage to the expected levels of endogenous adenosine.
C1 [Casado-Anguera, Veronica; Moreno, Estefania; Navarro, Gemma; Cortes, Antoni; Casado, Vicent] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain.
[Casado-Anguera, Veronica; Bonaventura, Jordi; Moreno, Estefania; Navarro, Gemma; Cortes, Antoni; Ferre, Sergi; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Casado-Anguera, Veronica; Moreno, Estefania; Navarro, Gemma; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Inst Biomed, E-08028 Barcelona, Spain.
[Bonaventura, Jordi; Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Casado-Anguera, V; Casado, V (reprint author), Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain.; Casado-Anguera, V; Casado, V (reprint author), Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.; Casado-Anguera, V; Casado, V (reprint author), Univ Barcelona, Inst Biomed, E-08028 Barcelona, Spain.
EM vcasadoanguera@gmail.com; vcasado@ub.edu
RI Ferre, Sergi/K-6115-2014;
OI Ferre, Sergi/0000-0002-1747-1779; Bonaventura, Jordi/0000-0002-4745-0151
FU Government of Catalonia [2014-SGR-1236]; Centro de Investigacion
Biomedica en Red sobre Enfermedades Neurodegenerativas [CB06/05/0064];
Spanish Ministerio de Economia y Competitividad [SAF2014-54840-R];
National Institute on Drug Abuse
FX This study was supported by the Government of Catalonia [grant number
2014-SGR-1236]; the Centro de Investigacion Biomedica en Red sobre
Enfermedades Neurodegenerativas [grant number CB06/05/0064]; the Spanish
Ministerio de Economia y Competitividad [grant number SAF2014-54840-R];
and by intramural funds of the National Institute on Drug Abuse.
NR 55
TC 3
Z9 3
U1 3
U2 6
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0300-5127
EI 1470-8752
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD APR 15
PY 2016
VL 44
BP 595
EP 600
DI 10.1042/BST20150276
PN 2
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DO1DF
UT WOS:000377518000040
PM 27068975
ER
PT J
AU Luna, A
Rajapakse, VN
Sousa, FG
Gao, JJ
Schultz, N
Varma, S
Reinhold, W
Sander, C
Pommier, Y
AF Luna, Augustin
Rajapakse, Vinodh N.
Sousa, Fabricio G.
Gao, Jianjiong
Schultz, Nikolaus
Varma, Sudhir
Reinhold, William
Sander, Chris
Pommier, Yves
TI rcellminer: exploring molecular profiles and drug response of the NCI-60
cell lines in R
SO BIOINFORMATICS
LA English
DT Article
AB Purpose: The rcellminer R package provides a wide range of functionality to help R users access and explore molecular profiling and drug response data for the NCI-60. The package enables flexible programmatic access to CellMiner's unparalleled breadth of NCI-60 data, including gene and protein expression, copy number, whole exome mutations, as well as activity data for 21K compounds, with information on their structure, mechanism of action and repeat screens. Functions are available to easily visualize compound structures, activity patterns and molecular feature profiles. Additionally, embedded R Shiny applications allow interactive data exploration.
C1 [Luna, Augustin; Sander, Chris] Mem Sloan Kettering Canc Ctr, Comp Biol Program, 1275 York Ave, New York, NY 10021 USA.
[Rajapakse, Vinodh N.; Varma, Sudhir; Reinhold, William; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sousa, Fabricio G.] Univ Fed Mato Grosso Do Sul, Ctr Estudos Celulas Tronco Terapia Celular & Gene, Programa Posgrad Farm, BR-79070900 Campo Grande, MS, Brazil.
[Gao, Jianjiong; Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, New York, NY 10021 USA.
RP Luna, A (reprint author), Mem Sloan Kettering Canc Ctr, Comp Biol Program, 1275 York Ave, New York, NY 10021 USA.; Rajapakse, VN; Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lunaa@cbio.mskcc.org; vinodh.rajapakse@nih.gov
RI Sousa, Fabricio/O-8878-2015
OI Sousa, Fabricio/0000-0003-0444-754X
FU NIH, MSKCC Genome Data Analysis Center [U24 CA143840]; Ruth L.
Kirschstein National Research Service Award [F32 CA192901]; Center for
Cancer Research, Intramural Program of the National Cancer Institute
[Z01 BC006150]
FX This work was supported by the NIH grants: MSKCC Genome Data Analysis
Center grant (U24 CA143840), the Ruth L. Kirschstein National Research
Service Award (F32 CA192901) and by the Center for Cancer Research,
Intramural Program of the National Cancer Institute (Z01 BC006150).
NR 8
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD APR 15
PY 2016
VL 32
IS 8
BP 1272
EP 1274
DI 10.1093/bioinformatics/btv701
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DJ8QJ
UT WOS:000374476800034
PM 26635141
ER
PT J
AU Machiela, MJ
Lan, Q
Slager, SL
Vermeulen, RCH
Teras, LR
Camp, NJ
Cerhan, JR
Spinelli, JJ
Wang, SS
Nieters, A
Vijai, J
Yeager, M
Wang, ZM
Ghesquieres, H
Mckay, J
Conde, L
de Bakker, PIW
Cox, DG
Burdett, L
Monnereau, A
Flowers, CR
De Roos, AJ
Brooks-Wilson, AR
Giles, GG
Melbye, M
Gu, J
Jackson, RD
Kane, E
Purdue, MP
Vajdic, CM
Albanes, D
Kelly, RS
Zucca, M
Bertrand, KA
Zeleniuch-Jacquotte, A
Lawrence, C
Hutchinson, A
Zhi, DG
Habermann, TM
Link, BK
Novak, AJ
Dogan, A
Asmann, YW
Liebow, M
Thompson, CA
Ansell, SM
Witzig, TE
Tille, H
Haioun, C
Molina, TJ
Hjalgrim, H
Glimelius, B
Adami, HO
Roos, G
Bracci, PM
Riby, J
Smith, MT
Holly, EA
Cozen, W
Hartge, P
Morton, LM
Severson, RK
Tinker, LF
North, KE
Becker, N
Benavente, Y
Boffetta, P
Brennan, P
Foretova, L
Maynadie, M
Staines, A
Lightfoot, T
Crouch, S
Smith, A
Roman, E
Diver, WR
Offit, K
Zelenetz, A
Klein, RJ
Villano, DJ
Zheng, TZ
Zhang, YW
Holford, TR
Turner, J
Southey, MC
Clavel, J
Virtamo, J
Weinstein, S
Riboli, E
Vineis, P
Kaaks, R
Boeing, H
Tjonneland, A
Angelucci, E
Di Lollo, S
Rais, M
De Vivo, I
Giovannucci, E
Kraft, P
Huang, JY
Ma, BS
Ye, YQ
Chiu, BCH
Liang, LM
Park, JH
Chung, CC
Weisenburger, DD
Fraumeni, JF
Salles, G
Glenn, M
Cannon-Albright, L
Curtin, K
Wu, XF
Smedby, KE
de Sanjose, S
Skibola, CF
Berndt, SI
Birmann, BM
Chanock, SJ
Rothman, N
AF Machiela, Mitchell J.
Lan, Qing
Slager, Susan L.
Vermeulen, Roel C. H.
Teras, Lauren R.
Camp, Nicola J.
Cerhan, James R.
Spinelli, John J.
Wang, Sophia S.
Nieters, Alexandra
Vijai, Joseph
Yeager, Meredith
Wang, Zhaoming
Ghesquieres, Herve
Mckay, James
Conde, Lucia
de Bakker, Paul I. W.
Cox, David G.
Burdett, Laurie
Monnereau, Alain
Flowers, Christopher R.
De Roos, Anneclaire J.
Brooks-Wilson, Angela R.
Giles, Graham G.
Melbye, Mads
Gu, Jian
Jackson, Rebecca D.
Kane, Eleanor
Purdue, Mark P.
Vajdic, Claire M.
Albanes, Demetrius
Kelly, Rachel S.
Zucca, Mariagrazia
Bertrand, Kimberly A.
Zeleniuch-Jacquotte, Anne
Lawrence, Charles
Hutchinson, Amy
Zhi, Degui
Habermann, Thomas M.
Link, Brian K.
Novak, Anne J.
Dogan, Ahmet
Asmann, Yan W.
Liebow, Mark
Thompson, Carrie A.
Ansell, Stephen M.
Witzig, Thomas E.
Tilly, Herve
Haioun, Corinne
Molina, Thierry J.
Hjalgrim, Henrik
Glimelius, Bengt
Adami, Hans-Olov
Roos, Goran
Bracci, Paige M.
Riby, Jacques
Smith, Martyn T.
Holly, Elizabeth A.
Cozen, Wendy
Hartge, Patricia
Morton, Lindsay M.
Severson, Richard K.
Tinker, Lesley F.
North, Kari E.
Becker, Nikolaus
Benavente, Yolanda
Boffetta, Paolo
Brennan, Paul
Foretova, Lenka
Maynadie, Marc
Staines, Anthony
Lightfoot, Tracy
Crouch, Simon
Smith, Alex
Roman, Eve
Diver, W. Ryan
Offit, Kenneth
Zelenetz, Andrew
Klein, Robert J.
Villano, Danylo J.
Zheng, Tongzhang
Zhang, Yawei
Holford, Theodore R.
Turner, Jenny
Southey, Melissa C.
Clavel, Jacqueline
Virtamo, Jarmo
Weinstein, Stephanie
Riboli, Elio
Vineis, Paolo
Kaaks, Rudolph
Boeing, Heiner
Tjonneland, Anne
Angelucci, Emanuele
Di Lollo, Simonetta
Rais, Marco
De Vivo, Immaculata
Giovannucci, Edward
Kraft, Peter
Huang, Jinyan
Ma, Baoshan
Ye, Yuanqing
Chiu, Brian C. H.
Liang, Liming
Park, Ju-Hyun
Chung, Charles C.
Weisenburger, Dennis D.
Fraumeni, Joseph F., Jr.
Salles, Gilles
Glenn, Martha
Cannon-Albright, Lisa
Curtin, Karen
Wu, Xifeng
Smedby, Karin E.
de Sanjose, Silvia
Skibola, Christine F.
Berndt, Sonja I.
Birmann, Brenda M.
Chanock, Stephen J.
Rothman, Nathaniel
TI Genetically predicted longer telomere length is associated with
increased risk of B-cell lymphoma subtypes
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; MENDELIAN
RANDOMIZATION; EPIDEMIOLOGIC RESEARCH; SUSCEPTIBILITY LOCI; CANCER-RISK;
HLA REGION; CLASSIFICATION; DYSFUNCTION; NEOPLASMS
AB Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
C1 [Machiela, Mitchell J.; Lan, Qing; Albanes, Demetrius; Hartge, Patricia; Morton, Lindsay M.; Weinstein, Stephanie; Chung, Charles C.; Fraumeni, Joseph F., Jr.; Berndt, Sonja I.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Slager, Susan L.; Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Habermann, Thomas M.; Novak, Anne J.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.] Mayo Clin, Dept Med, Rochester, MN USA.
[Asmann, Yan W.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Vermeulen, Roel C. H.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet & Epidemiol, Utrecht, Netherlands.
[Teras, Lauren R.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Camp, Nicola J.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA.
[Spinelli, John J.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Brooks-Wilson, Angela R.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Wang, Sophia S.] City Hope Beckman Res Inst, Div Canc Etiol, Duarte, CA USA.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Baden Wurttembe, Germany.
[Vijai, Joseph; Offit, Kenneth; Zelenetz, Andrew; Villano, Danylo J.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
[Yeager, Meredith; Wang, Zhaoming; Burdett, Laurie; Hutchinson, Amy] NCI, Div Canc Epidemiol & Genet, Canc Genom Res Lab, Gaithersburg, MD USA.
[Ghesquieres, Herve] Ctr Leon Berard, Canc Res Ctr Lyon, Dept Hematol, F-69373 Lyon, France.
[Cox, David G.] Ctr Leon Berard, Canc Res Ctr Lyon, INSERM U1052, F-69373 Lyon, France.
[Ghesquieres, Herve; Salles, Gilles] CNRS, UMR5239, Lab Biol Mol Cellule, Pierre Benite, France.
[Mckay, James] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Zhi, Degui] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Conde, Lucia; Riby, Jacques; Smith, Martyn T.; Skibola, Christine F.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Monnereau, Alain; Clavel, Jacqueline] Sorbonne Paris Cite, INSERM, Ctr Res Epidemiol & Stat, Epidemiol Childhood & Adolescent Canc Grp, Paris, France.
[Monnereau, Alain; Clavel, Jacqueline] Univ Paris 05, Paris, France.
[Monnereau, Alain] Inst Bergonie, Registre Hemopathies Malignes Gironde, Bordeaux, France.
[Flowers, Christopher R.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA.
[De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
[De Roos, Anneclaire J.; Tinker, Lesley F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Melbye, Mads; Hjalgrim, Henrik] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Melbye, Mads] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Gu, Jian; Ye, Yuanqing; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Kane, Eleanor; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Purdue, Mark P.] Ontario Hlth Study, Toronto, ON, Canada.
[Vajdic, Claire M.] Univ New S Wales, Ctr Big Data Res Hlth, Sydney, NSW, Australia.
[Kelly, Rachel S.; Bertrand, Kimberly A.; Adami, Hans-Olov; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kraft, Peter; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Zucca, Mariagrazia] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
[Rais, Marco] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy.
[Bertrand, Kimberly A.; De Vivo, Immaculata; Giovannucci, Edward; Birmann, Brenda M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA USA.
[Bertrand, Kimberly A.; De Vivo, Immaculata; Giovannucci, Edward; Birmann, Brenda M.] Harvard Univ, Sch Med, Boston, MA USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA.
[Zeleniuch-Jacquotte, Anne] NYU, Langone Med Ctr, Perlmutter Canc Ctr, New York, NY USA.
[Lawrence, Charles] WESTAT Corp, Rockville, MD 20850 USA.
[Link, Brian K.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Tilly, Herve] Univ Rouen, Ctr Henri Becquerel, Rouen, France.
[Haioun, Corinne] Henri Mondor Hosp, Lymphoid Malignancies Unit, Creteil, France.
[Haioun, Corinne] Univ Paris Est, Creteil, France.
[Molina, Thierry J.] Sorbonne Paris Cite, Univ Paris Descartes, AP HP, Dept Pathol,Necker Enfants Malad, Paris, France.
[Glimelius, Bengt] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Roos, Goran] Umea Univ, Dept Med Biosci, Umea, Sweden.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Becker, Nikolaus; Kaaks, Rudolph] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Baden Wurttembe, Germany.
[Benavente, Yolanda; de Sanjose, Silvia] Hosp Llobregat, Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona, Spain.
[Benavente, Yolanda; de Sanjose, Silvia] CIBERESP, CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Klein, Robert J.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Foretova, Lenka] Masaryk Mem Canc Inst & MF MU, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Maynadie, Marc] Univ Burgundy, Registre Hemopathies Malignes Cote Or, EA 4184, Dijon, France.
[Maynadie, Marc] Dijon Univ Hosp, Dijon, France.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[Zheng, Tongzhang; Zhang, Yawei] Yale Univ, Dept Environm Hlth Sci, New Haven, CT USA.
[Holford, Theodore R.] Yale Univ, Dept Biostat, New Haven, CT USA.
[Turner, Jenny] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Sydney, NSW, Australia.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.
[Vineis, Paolo] Human Genet Fdn, Turin, Italy.
[Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Angelucci, Emanuele] Osped Oncol Riferimento Reg A Businco, Hematol Unit, Cagliari, Italy.
[Di Lollo, Simonetta] Univ Florence, Sect Anatomopathol, Dept Surg & Translat Med, Florence, Italy.
[Ma, Baoshan] Dalian Maritime Univ, Coll Informat Sci & Technol, Dalian, Liaoning, Peoples R China.
[Chiu, Brian C. H.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Park, Ju-Hyun] Dongguk Univ, Dept Stat, Seoul, South Korea.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Salles, Gilles] Hosp Civils Lyon, Dept Hematol, Pierre Benite, France.
[Salles, Gilles] Univ Lyon 1, Dept Hematol, Pierre Benite, France.
[Smedby, Karin E.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.
RP Machiela, MJ (reprint author), 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM mitchell.machiela@nih.gov
RI de Sanjose Llongueras, Silvia/H-6339-2014; Flowers,
Christopher/F-1953-2010; Cox, David/A-2023-2009; Clavel,
Jacqueline/Q-2750-2016; Vermeulen, Roel/F-8037-2011; Brooks-Wilson,
Angela/E-9399-2012;
OI Flowers, Christopher/0000-0002-9524-3990; Cox,
David/0000-0002-2152-9259; Clavel, Jacqueline/0000-0002-3616-7676;
Vermeulen, Roel/0000-0003-4082-8163; Brooks-Wilson,
Angela/0000-0003-1009-6408; albright, lisa/0000-0003-2602-3668;
Machiela, Mitchell/0000-0001-6538-9705; Giles,
Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU Intramural Research Program of the NIH; National Cancer Institute; US
Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004];
National Cancer Institute, Department of Health and Human Services
[HHSN261201000006C]; American Cancer Society; Intramural Research
Program of the National Institutes of Health, NCI, Division of Cancer
Epidemiology and Genetics; National Cancer Institute Surveillance
Epidemiology and End Results program; European Commission
[QLK4-CT-2000-00422, FOOD-CT-2006-023103]; Spanish Ministry of Health
[PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10, RTIC
RD06/0020/0095]; Marato de TV3 Foundation [051210]; Agencia de
Gestiod'AjutsUniversitarisi de Recerca - Generalitat de Catalunya
[2014SRG756]; NIH [NO1-CO-12400]; Compagnia di San Paolo-Programma
Oncologia; Federal Office for Radiation Protection [StSch4261,
StSch4420]; Jose Carreras Leukemia Foundation [DJCLS-R12/23]; German
Federal Ministry for Education and Research [BMBF-01-EO-1303]; Health
Research Board, Ireland; Cancer Research Ireland; MH CZ - DRO (MMCI)
[00209805]; RECAMO [CZ.1.05/2.1.00/03.0101]; Fondation de France;
Association de Recherche Contre le Cancer; Leukemia & Lymphoma Society
Career Development Award; Bernstein Family Fund for Leukemia and
Lymphoma Research; National Institutes of Health [K08CA134919, CA167552,
CA149445, CA098122, CA098566, K07 CA115687, CA186107, CA87969, CA49449];
National Center for Advancing Translational Science [UL1 TR000135]; NCI
Specialized Programs of Research Excellence (SPORE) in Human Cancer [P50
CA97274]; Italian Association for Cancer Research (AIRC) [11855];
VicHealth and Cancer Council Victoria; Australian NHMRC [209057, 251553,
504711]; Geoffrey Beene Cancer Research Grant; Barbara K. Lipman
Lymphoma Research Fund [74419]; Intramural Research Program of the
National Cancer Institute, National Institutes of Health and Public
Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010,
N02-PC-71105]; Australian National Health and Medical Research Council
[ID990920]; Cancer Council NSW; University of Sydney Faculty of
Medicine; Intramural Research Program of the National Cancer Institute;
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS;
NCI, National Institutes of Health [CA1046282, CA154643]; California
Department of Health Services [103885]; National Cancer Institute's
Surveillance, Epidemiology, and End Results Program [HHSN261201000140C,
HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and
Prevention's National Program of Cancer Registries [1U58 DP000807-01];
Utah Population Database (UPDB); Utah Cancer Registry (UCR); Huntsman
Cancer Institute (HCI); HCI Cancer Center [P30 CA42014]; NIH from the
National Cancer Institute SEER Program [HHSN261201000026C]; Utah State
Department of Health; University of Utah; Yorkshire Cancer Research;
National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN271201100004C]; [006438]; [SP23-CT-2005-006438]
FX ATBC: This research was supported in part by the Intramural Research
Program of the NIH and the National Cancer Institute. Additionally, this
research was supported by US Public Health Service contracts
N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C from the
National Cancer Institute, Department of Health and Human Services.;
CPS-II: The Cancer Prevention Study II (CPS-II) Nutrition Cohort is
supported by the American Cancer Society. Genotyping for all CPS-II
samples were supported by the Intramural Research Program of the
National Institutes of Health, NCI, Division of Cancer Epidemiology and
Genetics. The authors would also like to acknowledge the contribution to
this study from central cancerregistries supported through the Centers
for Disease Control and Prevention National Program of Cancer
Registries, and Cancer Registries supported by the National Cancer
Institute Surveillance Epidemiology and End Results program.; EPIC:
Coordinated Action (contract #006438, SP23-CT-2005-006438); HuGeF (Human
Genetics Foundation), Torino, Italy; Cancer Research UK.; EpiLymph:
European Commission (grant references QLK4-CT-2000-00422 and
FOOD-CT-2006-023103); the Spanish Ministry of Health (grant references
CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10 and RTIC
RD06/0020/0095), the Marato de TV3 Foundation (grant reference 051210),
the Agencia de Gestiod'AjutsUniversitarisi de Recerca - Generalitat de
Catalunya (grant reference 2014SRG756) who had no role in the data
collection, analysis or interpretation of the results; the NIH (contract
NO1-CO-12400); the Compagnia di San Paolo-Programma Oncologia; the
Federal Office for Radiation Protection grants StSch4261 and StSch4420,
the Jose Carreras Leukemia Foundation grant DJCLS-R12/23, the German
Federal Ministry for Education and Research (BMBF-01-EO-1303); the
Health Research Board, Ireland and Cancer Research Ireland; Czech
Republic supported by MH CZ - DRO (MMCI, 00209805) and RECAMO,
CZ.1.05/2.1.00/03.0101; Fondation de France and Association de Recherche
Contre le Cancer.; GEC/Mayo GWAS: National Institutes of Health
(CA118444, CA148690 and CA92153). Intramural Research Program of the
NIH, National Cancer Institute. Veterans Affairs Research Service. Data
collection for Duke University was supported by a Leukemia & Lymphoma
Society Career Development Award, the Bernstein Family Fund for Leukemia
and Lymphoma Research, and the National Institutes of Health
(K08CA134919), National Center for Advancing Translational Science (UL1
TR000135).; HPFS: The HPFS was supported in part by the National
Institutes of Health grants CA167552, CA149445, CA098122, CA098566 and
K07 CA115687 (B.M.B.). We thank the participants and staff of the Health
Professionals Follow-up Study for their valuable contributions aswell as
the following state cancer registries for their help: AL, AZ, AR, CA,
CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ,
NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. The authors
assume full responsibility for analyses and interpretation of these
data.; Iowa-Mayo SPORE: NCI Specialized Programs of Research Excellence
(SPORE) in Human Cancer (P50 CA97274); National Cancer Institute (P30
CA086862 and P30 CA086862) and Henry J. Predolin Foundation.; Italian
GxE: Italian Association for Cancer Research (AIRC, Investigator Grant
11855) (PC); Fondazione Banco di Sardegna 20102012, and Regione Autonoma
della Sardegna (LR7 CRP-59812/2012) (MGE).; Mayo Clinic Case-Control:
National Institutes of Health (R01 CA92153) and National Cancer
Institute (P30 CA015083).; MCCS: The Melbourne Collaborative Cohort
Study recruitment was funded by VicHealth and Cancer Council Victoria.
The MCCS was further supported by Australian NHMRC grants 209057, 251553
and 504711 and by infrastructure provided by Cancer Council Victoria.
Cases and their vital status were ascertained through the Victorian
Cancer Registry (VCR) and the Australian Institute of Health and Welfare
(AIHW), including the National Death Index and the Australian Cancer
Database.; MSKCC: Geoffrey Beene Cancer Research Grant, Lymphoma
Foundation (LF5541); Barbara K. Lipman Lymphoma Research Fund (74419);
Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative
(57470); U01 HG007033; ENCODE; U01 HG007033.; NCI-SEER: Intramural
Research Program of the National Cancer Institute, National Institutes
of Health and Public Health Service (N01-PC-65064, N01-PC-67008,
N01-PC-67009, N01-PC-67010 and N02-PC-71105).; NHS: The NHS was
supported in part by National Institutes of Health grants CA186107,
CA87969, CA49449, CA149445, CA098122, CA098566 and K07 CA115687. We
thank the participants and staff of the Nurses' Health Study for their
valuable contributions as well as the following state cancer registries
for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY,
LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN,
TX, VA, WA and WY. The authors assume full responsibility for analyses
and interpretation of these data.; NSW: NSWwas supported by grants from
the Australian National Health and Medical Research Council (ID990920),
the Cancer Council NSW and the University of Sydney Faculty of
Medicine.; NYU-WHS: National Cancer Institute (R01 CA098661 and P30
CA016087); National Institute of Environmental Health Sciences
(ES000260).; PLCO: This research was supported by the Intramural
Research Program of the National Cancer Institute and by contracts from
the Division of Cancer Prevention, National Cancer Institute, NIH,
DHHS.; SCALE: Swedish Cancer Society (2009/659). Stockholm County
Council (20110209) and the Strategic Research Program in Epidemiology at
Karolinska Institute. Swedish Cancer Society grant (02 6661). National
Institutes of Health (5R01 CA69669-02); Plan Denmark.; UCSF2: The UCSF
studies were supported by the NCI, National Institutes of Health,
CA1046282 and CA154643. The collection of cancer incidence data used in
this study was supported by the California Department of Health Services
as part of the statewide cancer reporting program mandated by California
Health and Safety Code Section 103885; the National Cancer Institute's
Surveillance, Epidemiology, and End Results Program under contract
HHSN261201000140C awarded to the Cancer Prevention Institute of
California, contract HHSN261201000035C awarded to the University of
Southern California, and contract HHSN261201000034C awarded to the
Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
#1U58 DP000807-01 awarded to the Public Health Institute. The ideas and
opinions expressed here are those of the authors, and endorsement by the
State of California, the California Department of Health Services, the
National Cancer Institute or the Centers for Disease Control and
Prevention or their contractors and subcontractors is not intended nor
should be inferred.; UTAH: National Institutes of Health CA134674.
Partial support for data collection at the Utah site was made possible
by the Utah Population Database (UPDB) and the Utah Cancer Registry
(UCR). Partial support for all datasets within the UPDB is provided by
the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support
grant P30 CA42014. The UCR is supported in part by NIH contract
HHSN261201000026C from the National Cancer Institute SEER Program with
additional support from the Utah State Department of Health and the
University of Utah. Partial support for data collection in Sheffield,
UK, was made possible by funds from Yorkshire Cancer Research. We thank
the NCRI Haematooncology Clinical Studies Group, colleagues in the North
Trent Cancer Network the North Trent Haemato-oncology Database.; WHI:
WHI investigators are: Program Office-(National Heart, Lung, and Blood
Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale
Burwen, Joan McGowan, Leslie Ford and Nancy Geller; Clinical
Coordinating Center-(Fred Hutchinson Cancer Research Center, Seattle,
WA) Garnet Anderson, Ross Prentice, Andrea LaCroix and Charles
Kooperberg; Investigators and Academic Centers-(Brigham and Women's
Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar
Health Research Institute/Howard University, Washington, DC) Barbara V.
Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L.
Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson;
(University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson;
(University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University
of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University
of Iowa, Iowa City/Davenport, IA) RobertWallace; (University of
Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School
of Medicine, Winston-Salem, NC) Sally Shumaker; Women's Health
Initiative Memory Study( Wake Forest University School of Medicine,
Winston-Salem, NC) Sally Shumaker. The WHI program is funded by the
National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C and HHSN271201100004C.; YALE:
National Cancer Institute (CA62006) and National Cancer Institute
(CA165923).
NR 39
TC 5
Z9 5
U1 5
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 15
PY 2016
VL 25
IS 8
BP 1663
EP 1676
DI 10.1093/hmg/ddw027
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DJ5FE
UT WOS:000374231400016
PM 27008888
ER
PT J
AU Dorn, JF
Zhang, L
Phi, TT
Lacroix, B
Maddox, PS
Liu, J
Maddox, AS
AF Dorn, Jonas F.
Zhang, Li
Phi, Tan-Trao
Lacroix, Benjamin
Maddox, Paul S.
Liu, Jian
Maddox, Amy Shaub
TI A theoretical model of cytokinesis implicates feedback between membrane
curvature and cytoskeletal organization in asymmetric cytokinetic
furrowing
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID NONMUSCLE MYOSIN-II; CAENORHABDITIS-ELEGANS EMBRYO; CONTRACTILE RING;
ACTIN-FILAMENTS; FISSION YEAST; C-ELEGANS; CELL-DIVISION; ACTOMYOSIN
RING; CLEAVAGE FURROW; DIVIDING CELLS
AB During cytokinesis, the cell undergoes a dramatic shape change as it divides into two daughter cells. Cell shape changes in cytokinesis are driven by a cortical ring rich in actin filaments and nonmuscle myosin II. The ring closes via actomyosin contraction coupled with actin depolymerization. Of interest, ring closure and hence the furrow ingression are nonconcentric (asymmetric) within the division plane across Metazoa. This nonconcentricity can occur and persist even without preexisting asymmetric cues, such as spindle placement or cellular adhesions. Cell-autonomous asymmetry is not explained by current models. We combined quantitative high-resolution live-cell microscopy with theoretical modeling to explore the mechanistic basis for asymmetric cytokinesis in the Caenorhabditis elegans zygote, with the goal of uncovering basic principles of ring closure. Our theoretical model suggests that feedback among membrane curvature, cytoskeletal alignment, and contractility is responsible for asymmetric cytokinetic furrowing. It also accurately predicts experimental perturbations of conserved ring proteins. The model further suggests that curvature-mediated filament alignment speeds up furrow closure while promoting energy efficiency. Collectively our work underscores the importance of membrane-cytoskeletal anchoring and suggests conserved molecular mechanisms for this activity.
C1 [Dorn, Jonas F.; Zhang, Li; Phi, Tan-Trao] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada.
[Lacroix, Benjamin] Inst Jacques Monod, F-75205 Paris 13, France.
[Maddox, Paul S.; Maddox, Amy Shaub] Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA.
[Liu, Jian] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20814 USA.
[Dorn, Jonas F.] Novartis Pharma AG, CH-4056 Basel, Switzerland.
RP Maddox, AS (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA.; Liu, J (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20814 USA.
EM jian.liu@nih.gov; asm@unc.edu
FU Swiss National Science Foundation; National Institutes of Health
[GM102390]; National Heart, Lung, and Blood Institute at the National
Institutes of Health
FX We thank Kerry Bloom, Julie Canman, and Ewa Paluch for critical reading
of the manuscript. Carlos Patino Descovich and all members of the Maddox
labs provided discussion and support. Jean-Claude Labbe provided feeding
RNAs. James Fethiere (Institute for Research in Immunology and Cancer,
Montreal, Canada) provided purified protein fragments. We acknowledge
the thoughtful and constructive input from the anonymous referees.
J.F.D. was supported by a post-doctoral fellowship from the Swiss
National Science Foundation. This work was supported by National
Institutes of Health Grant GM102390 to A.S.M. J.L. is supported by the
intramural research program of the National Heart, Lung, and Blood
Institute at the National Institutes of Health.
NR 93
TC 0
Z9 0
U1 4
U2 7
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD APR 15
PY 2016
VL 27
IS 8
BP 1286
EP 1299
DI 10.1091/mbc.E15-06-0374
PG 14
WC Cell Biology
SC Cell Biology
GA DL6MP
UT WOS:000375753600012
PM 26912796
ER
PT J
AU Cekan, P
Hasegawa, K
Pan, Y
Tubman, E
Odde, D
Chen, JQ
Herrmann, MA
Kumar, S
Kalab, P
AF Cekan, Pavol
Hasegawa, Keisuke
Pan, Yu
Tubman, Emily
Odde, David
Chen, Jin-Qiu
Herrmann, Michelle A.
Kumar, Sheetal
Kalab, Petr
TI RCC1-dependent activation of Ran accelerates cell cycle and DNA repair,
inhibiting DNA damage-induced cell senescence
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID XENOPUS EGG EXTRACTS; NUCLEAR IMPORT; DRUG-RESISTANCE; CARGO TRANSPORT;
CANCER; EXPORT; PROTEINS; GRADIENT; MITOSIS; PROLIFERATION
AB The coordination of cell cycle progression with the repair of DNA damage supports the genomic integrity of dividing cells. The function of many factors involved in DNA damage response (DDR) and the cell cycle depends on their Ran GTPase-regulated nuclear-cytoplasmic transport (NCT). The loading of Ran with GTP, which is mediated by RCC1, the guanine nucleotide exchange factor for Ran, is critical for NCT activity. However, the role of RCC1 or Ran.GTP in promoting cell proliferation or DDR is not clear. We show that RCC1 overexpression in normal cells increased cellular Ran.GTP levels and accelerated the cell cycle and DNA damage repair. As a result, normal cells overexpressing RCC1 evaded DNA damage- induced cell cycle arrest and senescence, mimicking colorectal carcinoma cells with high endogenous RCC1 levels. The RCC1-induced inhibition of senescence required Ran and exportin 1 and involved the activation of importin beta-dependent nuclear import of 53BP1, a large NCT cargo. Our results indicate that changes in the activity of the Ran.GTP-regulated NCT modulate the rate of the cell cycle and the efficiency of DNA repair. Through the essential role of RCC1 in regulation of cellular Ran.GTP levels and NCT, RCC1 expression enables the proliferation of cells that sustain DNA damage.
C1 [Cekan, Pavol; Pan, Yu; Kumar, Sheetal; Kalab, Petr] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Chen, Jin-Qiu; Herrmann, Michelle A.] NCI, Collaborat Prot Technol Resource, NIH, Bethesda, MD 20892 USA.
[Hasegawa, Keisuke] Grinnell Coll, Dept Phys, Grinnell, IA 50112 USA.
[Hasegawa, Keisuke; Tubman, Emily; Odde, David] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA.
[Tubman, Emily; Odde, David] Univ Minnesota, Biomed Engn, Minneapolis, MN 55455 USA.
[Kalab, Petr] Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St, Baltimore, MD 21218 USA.
RP Kalab, P (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.; Kalab, P (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St, Baltimore, MD 21218 USA.
EM pkalab@yahoo.com
OI Odde, David/0000-0001-7731-2799
FU Center for Cancer Research, NCI; National Institutes of Health [R01
GM071522]
FX We thank R. Heald and K. Weis for comments and suggestions on the
manuscript; P. Scaffidi, B. Vogelstein, C. Harris, and A. Schetter for
cell lines, Karyopharm (Newton, MA) for the donation of KPT-330; and J.
Lee and S. J. Ryu for technical assistance. Imaging was performed at the
Confocal Microscopy Core Facility of the Center for Cancer Research,
National Cancer Institute (NCI), in Bethesda, Maryland. P. C., K.H.,
Y.P., J.-Q.C., M.A.H., S. K., and P. K. were supported by the Intramural
Research Program of the Center for Cancer Research, NCI. D.O. and E.T.
were supported by National Institutes of Health grant R01 GM071522.
NR 59
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U1 1
U2 4
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD APR 15
PY 2016
VL 27
IS 8
BP 1346
EP 1357
DI 10.1091/mbc.E16-01-0025
PG 12
WC Cell Biology
SC Cell Biology
GA DL6MP
UT WOS:000375753600017
PM 26864624
ER
PT J
AU Zerbe, CS
Marciano, BE
Katial, RK
Santos, CB
Adamo, N
Hsu, AP
Hanks, ME
Darnell, DN
Quezado, MM
Frein, C
Barnhart, LA
Anderson, VL
Uzel, G
Freeman, AF
Lisco, A
Nath, A
Major, EO
Sampaio, EP
Holland, SM
AF Zerbe, Christa S.
Marciano, Beatriz E.
Katial, Rohit K.
Santos, Carah B.
Adamo, Nick
Hsu, Amy P.
Hanks, Mary E.
Darnell, Dirk N.
Quezado, Martha M.
Frein, Cathleen
Barnhart, Lisa A.
Anderson, Victoria L.
Uzel, Gulbu
Freeman, Alexandra F.
Lisco, Andrea
Nath, Avindra
Major, Eugene O.
Sampaio, Elizabeth P.
Holland, Steven M.
TI Progressive Multifocal Leukoencephalopathy in Primary Immune
Deficiencies: Stat1 Gain of Function and Review of the Literature
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE progressive multifocal leukoencephalopathy; PML; primary
immunodeficiency; STAT1 gain of function; PID
ID COMMON VARIABLE IMMUNODEFICIENCY; CHRONIC MUCOCUTANEOUS CANDIDIASIS;
WISKOTT-ALDRICH SYNDROME; HYPER-IGM SYNDROME; JC-VIRUS;
MULTIPLE-SCLEROSIS; PATIENT; MUTATIONS; ADULT; CHILD
AB Background. Progressive multifocal leukoencephalopathy (PML) is a rare, severe, otherwise fatal viral infection of the white matter of the brain caused by the polyomavirus JC virus, which typically occurs only in immunocompromised patients. One patient with dominant gain-of-function (GOF) mutation in signal transducer and activator of transcription 1 (STAT1) with chronic mucocutaneous candidiasis and PML was reported previously. We aim to identify the molecular defect in 3 patients with PML and to review the literature on PML in primary immune defects (PIDs).
Methods. STAT1 was sequenced in 3 patients with PML. U3C cell lines were transfected with STAT1 and assays to search for STAT1 phosphorylation, transcriptional response, and target gene expression were performed.
Results. We identified 3 new unrelated cases of PML in patients with GOF STAT1 mutations, including the novel STAT1 mutation, L400Q. These STAT1 mutations caused delayed STAT1 dephosphorylation and enhanced interferon-gamma-driven responses. In our review of the literature regarding PML in primary immune deficiencies we found 26 cases, only 54% of which were molecularly characterized, the remainder being syndromically diagnosed only.
Conclusions. The occurrence of PML in 4 cases of STAT1 GOF suggests that STAT1 plays a critical role in the control of JC virus in the central nervous system.
C1 [Zerbe, Christa S.; Marciano, Beatriz E.; Adamo, Nick; Hsu, Amy P.; Hanks, Mary E.; Darnell, Dirk N.; Barnhart, Lisa A.; Anderson, Victoria L.; Uzel, Gulbu; Freeman, Alexandra F.; Lisco, Andrea; Sampaio, Elizabeth P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Katial, Rohit K.; Santos, Carah B.] Natl Jewish Hlth, Denver, CO USA.
[Katial, Rohit K.; Santos, Carah B.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Quezado, Martha M.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Frein, Cathleen] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Nath, Avindra] NINDS, Translat Neurosci Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Holland, SM (reprint author), NIH, Lab Clin Infect Dis, CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH); National
Cancer Institute, NIH [HHSN261200800001E]
FX This study was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH), and was funded in part with federal funds
from the National Cancer Institute, NIH (contract number
HHSN261200800001E).
NR 43
TC 4
Z9 4
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2016
VL 62
IS 8
BP 986
EP 994
DI 10.1093/cid/civ1220
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DK7EU
UT WOS:000375088500011
PM 26743090
ER
PT J
AU Calderon, MM
Penzak, SR
Pau, AK
Kumar, P
McManus, M
Alfaro, RM
Kovacs, JA
AF Calderon, Monica M.
Penzak, Scott R.
Pau, Alice K.
Kumar, Parag
McManus, Maryellen
Alfaro, Raul M.
Kovacs, Joseph A.
TI Efavirenz but Not Atazanavir/Ritonavir Significantly Reduces Atovaquone
Concentrations in HIV-Infected Subjects
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE atovaquone; efavirenz; drug interaction; Pneumocystis jiroveci
pneumonia; toxoplasma encephalitis
ID TOXOPLASMIC ENCEPHALITIS; PHARMACOKINETICS; LOPINAVIR/RITONAVIR;
VOLUNTEERS; LAMOTRIGINE; SUSPENSION; RITONAVIR; AIDS
AB Background. The current study was conducted to determine if efavirenz (EFV) or atazanavir/ritonavir (ATV/r)-based combination antiretroviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficiency virus (HIV)-infected patients receiving treatment doses of atovaquone.
Methods. Thirty HIV-infected volunteers were recruited, 10 taking no cART and 10 each taking cART that included EFV or ATV/r. Subjects were randomly assigned to atovaquone 750 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with a washout period in between. On day 14 of each phase, blood was sampled for pharmacokinetic studies, and the area under the concentration-time curve (AUCt) and average concentration (C-avg) were calculated and compared using an unpaired t test.
Results. Twenty-nine subjects completed both dosing cohorts. Subjects receiving EFV-based cART had 47% and 44% lower atovaquone AUCt than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respectively (P=.01). Only 5 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C-avg >15 mu g/mL, which has previously been associated with successful treatment of Pneumocystis jiroveci pneumonia. AUCt and C-avg did not significantly differ for concurrent ATV/r for 750 mg BID or 1500 mg BID when compared to the group not receiving cART. Nine of 10 subjects not receiving cART, 8 of 10 subjects receiving ATV/r, and 2 of 10 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C-avg >18.5 mu g/mL, a concentration that has previously been associated with successful treatment of Toxoplasma encephalitis (TE).
Conclusions. These data suggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate PCP may not be adequate in patients receiving concurrent EFV. Furthermore, doses lower than the currently recommended dose of 1500 mg BID may achieve plasma concentrations adequate to treat TE in HIV-infected patients not receiving EFV.
C1 [Calderon, Monica M.; Penzak, Scott R.; Kumar, Parag; Alfaro, Raul M.] NIH, Dept Pharm, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Calderon, Monica M.; McManus, Maryellen] NCI, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Pau, Alice K.] NIAID, NIH, Bethesda, MD USA.
[Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Calderon, Monica M.] US FDA, Off Safety & Epidemiol, Silver Spring, MD USA.
[Penzak, Scott R.] Univ North Texas Syst, Coll Pharm, Dept Pharmacotherapy, 3500 Camp Bowie Blvd,RES 411-A, Ft Worth, TX 76107 USA.
RP Penzak, SR (reprint author), Univ North Texas Syst, Coll Pharm, Dept Pharmacotherapy, 3500 Camp Bowie Blvd,RES 411-A, Ft Worth, TX 76107 USA.
EM scott.penzak@unthsc.edu
FU Intramural NIH HHS; PHS HHS [HHSN2612008000]
NR 17
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2016
VL 62
IS 8
BP 1036
EP 1042
DI 10.1093/cid/ciw028
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DK7EU
UT WOS:000375088500019
PM 26797214
ER
PT J
AU Lovely, GA
Sen, R
AF Lovely, Geoffrey A.
Sen, Ranjan
TI Evolving adaptive immunity
SO GENES & DEVELOPMENT
LA English
DT Editorial Material
DE RAG; Transib; V(D)J recombination; evolution; transposition
ID V(D)J RECOMBINATION; EVOLUTION; LOCUS; TRANSPOSITION; MECHANISM;
PROTEINS; SYSTEM; RAG2
AB Generation of a diverse repertoire of antigen receptor specificities via DNA recombination underpins adaptive immunity. In this issue of Genes & Development, Carmona and colleagues (pp. 909-917) provide novel insights into the origin and function of recombination-activating gene 1 (RAG1) and RAG2, the lymphocyte-specific components of the recombinase involved in the process.
C1 [Lovely, Geoffrey A.; Sen, Ranjan] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
RP Sen, R (reprint author), NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
EM senra@mail.nih.gov
NR 10
TC 0
Z9 0
U1 3
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD APR 15
PY 2016
VL 30
IS 8
BP 873
EP 875
DI 10.1101/gad.281014.116
PG 3
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DK4XL
UT WOS:000374923500001
PM 27083993
ER
PT J
AU Ghirlando, R
Felsenfeld, G
AF Ghirlando, Rodolfo
Felsenfeld, Gary
TI CTCF: making the right connections
SO GENES & DEVELOPMENT
LA English
DT Review
DE chromatin; insulators; topologically associated domains
ID ENHANCER-BLOCKING ACTIVITY; INSULATOR PROTEIN CTCF; 3D GENOME
ARCHITECTURE; CCCTC-BINDING FACTOR; C-MYC GENE; TRANSCRIPTIONAL
INSULATION; CHROMATIN ARCHITECTURE; MEDIATED INTERACTIONS; REGULATORY
LANDSCAPE; PLURIPOTENT CELLS
AB The role of the zinc finger protein CTCF in organizing the genome within the nucleus is now well established. Widely separated sites on DNA, occupied by both CTCF and the cohesin complex, make physical contacts that create large loop domains. Additional contacts between loci within those domains, often also mediated by CTCF, tend to be favored over contacts between loci in different domains. A large number of studies during the past 2 years have addressed the questions: How are these loops generated? What are the effects of disrupting them? Are there rules governing large-scale genome organization? It now appears that the strongest and evolutionarily most conserved of these CTCF interactions have specific rules for the orientation of the paired CTCF sites, implying the existence of a nonequilibrium mechanism of generation. Recent experiments that invert, delete, or inactivate one of a mating CTCF pair result in major changes in patterns of organization and gene expression in the surrounding regions. What remain to be determined are the detailed molecular mechanisms for re-establishing loop domains and maintaining them after replication and mitosis. As recently published data show, some mechanisms may involve interactions with noncoding RNAs as well as protein cofactors. Many CTCF sites are also involved in other functions such as modulation of RNA splicing and specific regulation of gene expression, and the relationship between these activities and loop formation is another unanswered question that should keep investigators occupied for some time.
C1 [Ghirlando, Rodolfo; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gary.felsenfeld@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX We thank members of our laboratory for their suggestions and
encouragement. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.
NR 94
TC 11
Z9 11
U1 14
U2 29
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD APR 15
PY 2016
VL 30
IS 8
BP 881
EP 891
DI 10.1101/gad.277863.116
PG 11
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DK4XL
UT WOS:000374923500004
PM 27083996
ER
PT J
AU Jennis, M
Kung, CP
Basu, S
Budina-Kolomets, A
Leu, JIJ
Khaku, S
Scott, JP
Cai, KQ
Campbell, MR
Porter, DK
Wang, XT
Bell, DA
Li, XX
Garlick, DS
Liu, Q
Hollstein, M
George, DL
Murphy, ME
AF Jennis, Matthew
Kung, Che-Pei
Basu, Subhasree
Budina-Kolomets, Anna
Leu, Julia I-Ju
Khaku, Sakina
Scott, Jeremy P.
Cai, Kathy Q.
Campbell, Michelle R.
Porter, Devin K.
Wang, Xuting
Bell, Douglas A.
Li, Xiaoxian
Garlick, David S.
Liu, Qin
Hollstein, Monica
George, Donna L.
Murphy, Maureen E.
TI An African-specific polymorphism in the TP53 gene impairs p53 tumor
suppressor function in a mouse model
SO GENES & DEVELOPMENT
LA English
DT Article
DE p53; tumor suppression; metabolism; ferroptosis; polymorphism; Ser46
phosphorylation
ID INTERACTING PROTEIN KINASE-2; NONAPOPTOTIC CELL-DEATH; DNA-DAMAGE;
P53-DEPENDENT APOPTOSIS; SER46 PHOSPHORYLATION; FERROPTOSIS; MUTATIONS;
MICE; SENESCENCE; RESPONSES
AB A nonsynonymous single-nucleotide polymorphism at codon 47 in TP53 exists in African-descent populations (P47S, rs1800371; referred to here as S47). Here we report that, in human cell lines and a mouse model, the S47 variant exhibits a modest decrease in apoptosis in response to most genotoxic stresses compared with wild-type p53 but exhibits a significant defect in cell death induced by cisplatin. We show that, compared with wild-type p53, S47 has nearly indistinguishable transcriptional function but shows impaired ability to transactivate a subset of p53 target genes, including two involved in metabolism: Gls2 (glutaminase 2) and Sco2. We also show that human and mouse cells expressing the S47 variant are markedly resistant to cell death by agents that induce ferroptosis (iron-mediated nonapoptotic cell death). We show that mice expressing S47 in homozygous or heterozygous form are susceptible to spontaneous cancers of diverse histological types. Our data suggest that the S47 variant may contribute to increased cancer risk in individuals of African descent, and our findings highlight the need to assess the contribution of this variant to cancer risk in these populations. These data also confirm the potential relevance of metabolism and ferroptosis to tumor suppression by p53.
C1 [Jennis, Matthew; Kung, Che-Pei; Basu, Subhasree; Budina-Kolomets, Anna; Khaku, Sakina; Scott, Jeremy P.; Liu, Qin; Murphy, Maureen E.] Wistar Inst Anat & Biol, Program Mol & Cellular Oncogenesis, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Jennis, Matthew] Drexel Univ, Coll Med, Program Mol & Cellular Biol & Genet, Philadelphia, PA 19102 USA.
[Leu, Julia I-Ju; George, Donna L.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Cai, Kathy Q.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Campbell, Michelle R.; Porter, Devin K.; Wang, Xuting; Bell, Douglas A.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Li, Xiaoxian] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Garlick, David S.] Wistar Inst Anat & Biol, Ctr Canc, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Hollstein, Monica] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England.
RP Murphy, ME (reprint author), Wistar Inst Anat & Biol, Program Mol & Cellular Oncogenesis, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM mmurphy@wistar.org
OI Wang, Xuting/0000-0001-6781-8008
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01-ES-100475]; [R01
CA102184]; [PO1 CA114046]
FX We acknowledge the Cell Culture Facility and Transgenic Facility at The
Fox Chase Cancer Center as well as the members of the Microscopy
Facility (Fred Keeney), the Genomics Facility (Tran Nguyen and Celia
Chang), and the Laboratory Animal Facility at The Wistar Institute for
assistance with these studies. Support for Core Facilities used in this
study was provided by Cancer Center Support Grant (CCSG) CA010815 to The
Wistar Institute. This research was funded by R01 CA102184 (M.E.M.) and
PO1 CA114046 (to D.L.G). This work was supported in part by funding from
the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health
Z01-ES-100475 (to D.A.B.). M.J., C.-P.K., S.B., A.B.-K., J.I.-J.L.,
D.A.B., Q.L., M.H., D.L.G., and M.E.M. conceived and designed the study.
K.Q.C., X.L., D.S.G., and M.H. provided reagents and expertise. M.J.,
C.-P.K., S.B., A.B.-K., J.I.-J.L., S.K., J.P.S., M.R.C., D.K.P., X.W.,
D.A.B., Q.L., M.H., D.L.G., and M.E.M. acquired and analyzed the data.
M.J., D.L.G., and M.E.M. drafted the manuscript, and all authors
provided critical revisions.
NR 41
TC 6
Z9 6
U1 0
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD APR 15
PY 2016
VL 30
IS 8
BP 918
EP 930
DI 10.1101/gad.275891.115
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DK4XL
UT WOS:000374923500007
PM 27034505
ER
PT J
AU Aerbajinai, W
Liu, LH
Zhu, JQ
Kumkhaek, C
Chin, K
Rodgers, GP
AF Aerbajinai, Wulin
Liu, Lunhua
Zhu, Jianqiong
Kumkhaek, Chutima
Chin, Kyung
Rodgers, Griffin P.
TI Glia Maturation Factor- Regulates Monocyte Migration through Modulation
of 1-Integrin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE adhesion; Arp2; 3 complex; cell migration; endocytosis; integrin;
ubiquitylation (ubiquitination); glia maturation factor-gamma (GMFG)
ID STIMULATED GLUT4 TRANSLOCATION; CELL-MIGRATION; MEMBRANE-FUSION;
FACTOR-GAMMA; NEUTROPHIL CHEMOTAXIS; LYSOSOMAL DEGRADATION; SYNIP
PHOSPHORYLATION; ACTIN POLYMERIZATION; INTEGRIN TRAFFICKING; RECYCLING
PATHWAYS
AB Monocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle, but the complex molecular mechanisms underlying this process have not been fully elucidated. Glia maturation factor- (GMFG), a novel regulator of the Arp2/3 complex, has been shown to regulate directional migration of neutrophils and T-lymphocytes. In this study, we explored the important role of GMFG in monocyte chemotaxis, adhesion, and 1-integrin turnover. We found that knockdown of GMFG in monocytes resulted in impaired chemotactic migration toward formyl-Met-Leu-Phe (fMLP) and stromal cell-derived factor 1 (SDF-1) as well as decreased 51-integrin-mediated chemoattractant-stimulated adhesion. These GMFG knockdown impaired effects could be reversed by cotransfection of GFP-tagged full-length GMFG. GMFG knockdown cells reduced the cell surface and total protein levels of 51-integrin and increased its degradation. Importantly, we demonstrate that GMFG mediates the ubiquitination of 1-integrin through knockdown or overexpression of GMFG. Moreover, GMFG knockdown retarded the efficient recycling of 1-integrin back to the plasma membrane following normal endocytosis of 51-integrin, suggesting that the involvement of GMFG in maintaining 51-integrin stability may occur in part by preventing ubiquitin-mediated degradation and promoting 1-integrin recycling. Furthermore, we observed that GMFG interacted with syntaxin 4 (STX4) and syntaxin-binding protein 4 (STXBP4); however, only knockdown of STXBP4, but not STX4, reduced monocyte migration and decreased 1-integrin cell surface expression. Knockdown of STXBP4 also substantially inhibited 1-integrin recycling in human monocytes. These results indicate that the effects of GMFG on monocyte migration and adhesion probably occur through preventing ubiquitin-mediated proteasome degradation of 51-integrin and facilitating effective 1-integrin recycling back to the plasma membrane.
C1 [Aerbajinai, Wulin; Zhu, Jianqiong; Kumkhaek, Chutima; Chin, Kyung; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Lunhua] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NIH, Mol & Clin Hematol Branch, Bldg 10,Rm 9N-113A, Bethesda, MD 20892 USA.
EM gr5n@nih.gov
FU NIDDK, National Institutes of Health
FX This work was supported by the Intramural Research Program of NIDDK,
National Institutes of Health. The authors declare that they have no
conflicts of interest with the contents of this article. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 62
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 15
PY 2016
VL 291
IS 16
BP 8549
EP 8564
DI 10.1074/jbc.M115.674200
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK2VT
UT WOS:000374773200020
PM 26895964
ER
PT J
AU Jang, SI
Ong, HL
Liu, X
Alevizos, I
Ambudkar, IS
AF Jang, Shyh-Ing
Ong, Hwei Ling
Liu, Xibao
Alevizos, Ilias
Ambudkar, Indu S.
TI Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of
Activated T Cells Promote the Acinar Phenotype of the Primary Human
Salivary Gland Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE calcium release-activated calcium channel protein 1 (ORAI1); gene
expression; NFAT transcription factor; stromal interaction molecule 1
(STIM1); water channel
ID NEURAL STEM-CELLS; EPITHELIAL-CELLS; TRANSCRIPTION FACTORS; CALCIUM
SIGNALS; GROWTH-FACTOR; SECRETION; NFAT; DIFFERENTIATION; EXPRESSION;
CHANNELS
AB The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca2+] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca2+-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca2+ entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca2+-dependent up-regulation of AQP5. These important findings reveal that the Ca2+-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture.
C1 [Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.] NIDCR, Secretory & Physiol Sect, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA.
[Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.] NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Alevizos, I; Ambudkar, IS (reprint author), NIDCR, Secretory & Physiol Sect, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA.; Alevizos, I; Ambudkar, IS (reprint author), NIDCR, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM alevizosi@nidcr.nih.gov; indu.ambudkar@nih.gov
NR 37
TC 3
Z9 3
U1 2
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 15
PY 2016
VL 291
IS 16
BP 8709
EP 8720
DI 10.1074/jbc.M115.701607
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK2VT
UT WOS:000374773200033
PM 26903518
ER
PT J
AU Randles, L
Anchoori, RK
Roden, RBS
Walters, KJ
AF Randles, Leah
Anchoori, Ravi K.
Roden, Richard B. S.
Walters, Kylie J.
TI The Proteasome Ubiquitin Receptor hRpn13 and Its Interacting
Deubiquitinating Enzyme Uch37 Are Required for Proper Cell Cycle
Progression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE cancer biology; cell proliferation; proteasome; ubiquitin;
ubiquitylation (ubiquitination); RA190; Uch37; cell cycle progression;
hRpn13; p27Kip1
ID CDK INHIBITOR P27; 26S PROTEASOME; BORTEZOMIB RESISTANCE; REGULATORY
PARTICLE; ANTICANCER THERAPY; MULTIPLE-MYELOMA; SUBUNIT; CANCER; RPN13;
ACTIVATION
AB Recently, we reported that bisbenzylidine piperidone RA190 adducts to Cys-88 of the proteasome ubiquitin receptor hRpn13, triggering accumulation of ubiquitinated proteins and endoplasmic reticulum stress-related apoptosis in various cancer cell lines. hRpn13 contains an N-terminal pleckstrin-like receptor for ubiquitin domain that binds ubiquitin and docks it into the proteasome as well as a C-terminal deubiquitinase adaptor (DEUBAD) domain that binds the deubiquitinating enzyme Uch37. Here we report that hRpn13 and Uch37 are required for proper cell cycle progression and that their protein knockdown leads to stalling at G(0)/G(1). Moreover, serum-starved cells display reduced hRpn13 and Uch37 protein levels with hallmarks of G(0)/G(1) stalling and recovery to their steady-state protein levels following release from nutrient deprivation. Interestingly, loss of hRpn13 correlates with a small but statistically significant reduction in Uch37 protein levels, suggesting that hRpn13 interaction may stabilize this deubiquitinating enzyme in human cells. We also find that RA190 treatment leads to a loss of S phase, suggesting a block of DNA replication, and G(2) arrest by using fluorescence-activated cell sorting. Uch37 deprivation further indicated a reduction of DNA replication and G(0)/G(1) stalling. Overall, this work implicates hRpn13 and Uch37 in cell cycle progression, providing a rationale for their function in cellular proliferation and for the apoptotic effect of the hRpn13-targeting molecule RA190.
C1 [Randles, Leah; Walters, Kylie J.] NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Anchoori, Ravi K.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Gynecol & Obstet, Baltimore, MD 21231 USA.
RP Walters, KJ (reprint author), NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
EM kylie.walters@nih.gov
FU NCI, National Institutes of Health Center for Cancer Research; NCI,
National Institutes of Health [P50 CA098252]; Alleghany Health
Network-Johns Hopkins Cancer Research Fund; PI therapeutics
FX This work was supported by the Intramural Research Program of the NCI,
National Institutes of Health Center for Cancer Research (to K. J. W.),
NCI, National Institutes of Health Grant P50 CA098252 (to R. B. S. R.),
and the Alleghany Health Network-Johns Hopkins Cancer Research Fund (to
R. B. S. R.). R. K. A. and R. B. S. R. are inventors of intellectual
property licensed to Pontifax/PI therapeutics and have received research
funding from PI therapeutics. Under a licensing agreement between
Pontifax/PI therapeutics and the Johns Hopkins University, Drs. Roden
and Anchoori are entitled to a share of royalty received by the
University on an invention described in this article. The terms of this
arrangement are being managed by the Johns Hopkins University in
accordance with its conflict of interest policies. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 77
TC 2
Z9 2
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 15
PY 2016
VL 291
IS 16
BP 8773
EP 8783
DI 10.1074/jbc.M115.694588
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK2VT
UT WOS:000374773200038
PM 26907685
ER
PT J
AU Pettitt, J
Higgs, ES
Adams, RD
Jahrling, PB
Hensley, LE
AF Pettitt, James
Higgs, Elizabeth S.
Adams, Rick D.
Jahrling, Peter B.
Hensley, Lisa E.
TI Use of Existing Diagnostic Reverse-Transcription Polymerase Chain
Reaction Assays for Detection of Ebola Virus RNA in Semen
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Ebola; PCR; semen; diagnosis
ID TRANSMISSION
AB Sexual transmission of Ebola virus in Liberia has now been documented and associated with new clusters in regions previously declared Ebola free. Assays that have Emergency Use Authorization (EUA) and are routinely used to detect Ebola virus RNA in whole blood and plasma specimens at the Liberian Institute for Biomedical Research were tested for their suitability in detecting the presence of Ebola virus RNA in semen. Qiagen AVL extraction protocols, as well as the Ebola Zaire Target 1 and major groove binder quantitative reverse-transcription polymerase chain reaction assays, were demonstrably suitable for this purpose and should facilitate epidemiologic investigations, including those involving long-term survivors of Ebola.
C1 [Pettitt, James; Higgs, Elizabeth S.; Adams, Rick D.; Jahrling, Peter B.; Hensley, Lisa E.] NIAID, Integrated Res Facil, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
RP Jahrling, PB (reprint author), NIAID, Integrated Res Facil, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM jahrlingp@niaid.nih.gov
FU intramural program of the Division of Clinical Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by the intramural program of the Division of
Clinical Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 7
TC 6
Z9 6
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2016
VL 213
IS 8
BP 1237
EP 1239
DI 10.1093/infdis/jiv454
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DL0CG
UT WOS:000375298700006
PM 26374912
ER
PT J
AU Akbar, M
Essa, MM
Daradkeh, G
Abdelmegeed, MA
Choi, Y
Mahmood, L
Song, BJ
AF Akbar, Mohammed
Essa, Musthafa Mohamed
Daradkeh, Ghazi
Abdelmegeed, Mohamed A.
Choi, Youngshim
Mahmood, Lubna
Song, Byoung-Joon
TI Mitochondrial dysfunction and cell death in neurodegenerative diseases
through nitroxidative stress
SO BRAIN RESEARCH
LA English
DT Article
DE Oxidative stress; Mitochondrial dysfunction; Neuronal cell death;
Neurodegenerative diseases; Post-translational protein modifications;
Antioxidants; Translational research
ID TRAUMATIC BRAIN-INJURY; NITRIC-OXIDE SYNTHASE; TARGETED ANTIOXIDANT
MITOQ; ACUTE LIVER-INJURY; DEPENDENT NEUROPROTECTIVE PROTEIN;
AMYOTROPHIC-LATERAL-SCLEROSIS; MILD COGNITIVE IMPAIRMENT; TRANSGENIC
MOUSE MODEL; AMYLOID-BETA PEPTIDE; ALZHEIMERS-DISEASE
AB Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities. Published by Elsevier B.V.
C1 [Akbar, Mohammed; Abdelmegeed, Mohamed A.; Choi, Youngshim; Song, Byoung-Joon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Essa, Musthafa Mohamed; Daradkeh, Ghazi] Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman.
[Essa, Musthafa Mohamed] Sultan Qaboos Univ, Ageing & Dementia Res Grp, Muscat, Oman.
[Mahmood, Lubna] Qatar Univ, Dept Nutr Sci, Muscat, Qatar.
RP Akbar, M; Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.; Essa, MM (reprint author), Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman.
FU National Institute on Alcohol Abuse and Alcoholism; Research Council,
Oman [RC/AGR/FOOD/11/01]; Sultan Qaboos University, Oman
[IG/AGR/FOOD/14/01]; KRIBB Research Initiative Program (Korean
Biomedical Scientist Fellowship Program), Korea Research Institute of
Bioscience and Biotechnology, Republic of Korea
FX The work is supported by the Intramural Program Fund of the National
Institute on Alcohol Abuse and Alcoholism. The authors (MME and GD) also
highly appreciate the research supports from the Research Council, Oman
(RC/AGR/FOOD/11/01 to MME) and the internal grant (IG/AGR/FOOD/14/01)
from Sultan Qaboos University, Oman. Youngshim Choi is supported by the
KRIBB Research Initiative Program (Korean Biomedical Scientist
Fellowship Program), Korea Research Institute of Bioscience and
Biotechnology, Republic of Korea.
NR 270
TC 6
Z9 8
U1 8
U2 28
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD APR 15
PY 2016
VL 1637
BP 34
EP 55
DI 10.1016/j.brainres.2016.02.016
PG 22
WC Neurosciences
SC Neurosciences & Neurology
GA DK0NY
UT WOS:000374610700004
PM 26883165
ER
PT J
AU Liu, BJ
Chen, HL
Fang, F
Tillander, A
Wirdefeldt, K
AF Liu, Bojing
Chen, Honglei
Fang, Fang
Tillander, Annika
Wirdefeldt, Karin
TI Early-Life Factors and Risk of Parkinson's Disease: A Register-Based
Cohort Study
SO PLOS ONE
LA English
DT Article
ID EXPOSURE; CHILDHOOD; INFLUENZA; EPIDEMIOLOGY; ASSOCIATION; INFECTIONS;
SIBLINGS
AB Parkinson's disease (PD) may take decades to develop and early life exposures such as infection may be important. However, few epidemiological studies have evaluated early life risk factors in relation to PD risk. We therefore examined such associations in a prospective analysis of 3 545 612 individuals born in Sweden between 1932 and 1970 without PD on January 1, 2002. Incident PD cases were identified using the Swedish Patient Register during 2002-2010. Information on sibship size, number of older and younger siblings, multiple births, parental age, birth month and season was obtained from the Swedish Multi-Generation Register. Monthly data on national burden of influenza-like illness during 1932-1970 were obtained from the Swedish Public Health Agency. Hazard ratios with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. During the follow-up, 8779 incident PD cases were identified. As expected, older age, male sex, parental occupation as farmers, and family history of PD were associated with higher PD risk. Overall, early life factors, including flu burden in the year of birth, were not associated with PD risk, although we did find a lower PD risk among participants with older siblings than those without (HR = 0.93, 95% CI: 0.89, 0.98). Our study therefore provided little support for important etiological contributions of early life factors to the PD risk late in life. The finding of a lower PD risk among individuals with older siblings will need confirmation and further investigation.
C1 [Liu, Bojing; Fang, Fang; Tillander, Annika; Wirdefeldt, Karin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
RP Liu, BJ (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
EM bojing.liu@ki.se
OI Chen, Honglei/0000-0003-3446-7779
FU Swedish Research Council for Health, Working Life and Welfare
[2013-1350]; KI-NIH Doctoral Partnership Program in Neuroscience;
Swedish Society for Medical Research; Karolinska Institutet; NIH, the
National Institute of Environmental Health Sciences [Z01-ES-101986]
FX KW received funding from Swedish Research Council for Health, Working
Life and Welfare (www.forte.se, 2013-1350), KI-NIH Doctoral Partnership
Program in Neuroscience (www.ki.se). FF received funding from Swedish
Society for Medical Research (www.ssmf.se) and Karolinska Institutet
(www.ki.se). HC received funding from the intramural research program of
the NIH, the National Institute of Environmental Health Sciences
(www.niehs.nih.gov, Z01-ES-101986). The funders had no role in the
design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
manuscript; or decision to submit the manuscript for publication.
NR 29
TC 1
Z9 1
U1 2
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 15
PY 2016
VL 11
IS 4
AR e0152841
DI 10.1371/journal.pone.0152841
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ6AH
UT WOS:000374291800010
PM 27082111
ER
PT J
AU Zhao, Z
Zhu, XP
Cui, K
Mancuso, J
Federley, R
Fischer, K
Teng, GJ
Mittal, V
Gao, DC
Zhao, H
Wong, STC
AF Zhao, Zhen
Zhu, Xiaoping
Cui, Kemi
Mancuso, James
Federley, Richard
Fischer, Kari
Teng, Gao-jun
Mittal, Vivek
Gao, Dingcheng
Zhao, Hong
Wong, Stephen T. C.
TI In Vivo Visualization and Characterization of Epithelial-Mesenchymal
Transition in Breast Tumors
SO CANCER RESEARCH
LA English
DT Article
ID ALTERNATIVE SPLICING REPORTERS; CANCER METASTASIS; C-MET; PLASTICITY;
GROWTH; ANGIOGENESIS; FIBROBLASTS; PROGRESSION; INHIBITION; MICROSCOPY
AB The activation of the epithelial-to-mesenchymal transition (EMT) program is a critical step in cancer progression and metastasis, but visualization of this process at the single-cell level, especially in vivo, remains challenging. We established an in vivo approach to track the fate of tumor cells based on a novel EMT-driven fluorescent color switching breast cancer mouse model and intravital two-photon laser scanning microscopy. Specifically, the MMTV-PyMT, Rosa26-RFP-GFP, and Fsp1-Cre triple transgenic mouse model was used to monitor the conversion of RFP-positive epithelial cells to GFP-positive mesenchymal cells in mammary tumors under the control of the Fsp1 (ATL1) promoter, a gatekeeper of EMT initiation. RFP-positive cells were isolated from the tumors, sorted, and transplanted into mammary fat pads of SCID mice to monitor EMT during breast tumor formation. We found that the conversion from RFP-to-GFP-positive and spindle-shaped cells was a gradual process, and that GFP-positive cells preferentially localized close to blood vessels, independent of tumor size. Furthermore, cells undergoing EMT expressed high levels of the HGF receptor, c-Met, and treatment of RFP-positive cells with the c-Met inhibitor, cabozantinib, suppressed the RFP-to-GFP conversion in vitro. Moreover, administration of cabozantinib to mice with palpable RFP-positive tumors resulted in a silent EMT phenotype whereby GFP-positive cells exhibited reduced motility, leading to suppressed tumor growth. In conclusion, our imaging technique provides a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. (C) 2016 AACR.
C1 [Zhao, Zhen; Teng, Gao-jun; Wong, Stephen T. C.] Southeast Univ, Zhong Da Hosp, Dept Radiol, Nanjing, Jiangsu, Peoples R China.
[Zhao, Zhen; Zhu, Xiaoping; Cui, Kemi; Mancuso, James; Federley, Richard; Zhao, Hong; Wong, Stephen T. C.] Weill Cornell Med, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX USA.
[Fischer, Kari; Mittal, Vivek; Gao, Dingcheng] Weill Cornell Med, Dept Cell & Dev Biol, New York, NY USA.
[Zhao, Hong; Wong, Stephen T. C.] Weill Cornell Med, NCI Ctr Modeling Canc Dev, Houston Methodist Res Inst, Houston, TX USA.
[Wong, Stephen T. C.] Houston Methodist Hosp, Houston Methodist Canc Ctr, Houston, TX USA.
RP Wong, STC (reprint author), Southeast Univ, Zhong Da Hosp, Dept Radiol, Nanjing, Jiangsu, Peoples R China.; Zhao, H; Wong, STC (reprint author), Weill Cornell Med, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX USA.; Zhao, H; Wong, STC (reprint author), Weill Cornell Med, NCI Ctr Modeling Canc Dev, Houston Methodist Res Inst, Houston, TX USA.; Wong, STC (reprint author), Houston Methodist Hosp, Houston Methodist Canc Ctr, Houston, TX USA.; Zhao, H (reprint author), Houston Methodist Res Inst, 6670 Bertner Ave, Houston, TX 77030 USA.
EM hzhao@houstonmethodist.org; stwong@houstonmethodist.org
FU NCI NIH HHS [U01 CA188388, U54 CA149196]
NR 36
TC 7
Z9 7
U1 5
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2094
EP 2104
DI 10.1158/0008-5472.CAN-15-2662
PG 11
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700008
PM 26893478
ER
PT J
AU Cherkasova, E
Scrivani, C
Doh, S
Weisman, Q
Takahashi, Y
Harashima, N
Yokoyama, H
Srinivasan, R
Linehan, WM
Lerman, MI
Childs, RW
AF Cherkasova, Elena
Scrivani, Claire
Doh, Susan
Weisman, Quinn
Takahashi, Yoshiyuki
Harashima, Nanae
Yokoyama, Hisayuki
Srinivasan, Ramaprasad
Linehan, W. Marston
Lerman, Michael I.
Childs, Richard W.
TI Detection of an Immunogenic HERV-E Envelope with Selective Expression in
Clear Cell Kidney Cancer
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN ENDOGENOUS RETROVIRUS; BREAST-CANCER; T-LYMPHOCYTES;
TRANSFORMATION; MELANOMA; SEQUENCE; ANTIGEN; TRANSCRIPTS; PROTEIN; LINES
AB VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript-stimulated CD8(+) T cells, which could recognize HLA-A*0201-positive HERV-E-expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell-based immunotherapy of kidney cancer. (C) 2016 AACR.
C1 [Cherkasova, Elena; Scrivani, Claire; Doh, Susan; Weisman, Quinn; Takahashi, Yoshiyuki; Harashima, Nanae; Yokoyama, Hisayuki; Lerman, Michael I.; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Srinivasan, Ramaprasad; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Takahashi, Yoshiyuki] Nagoya Univ, Grad Sch Med, Dept Pediat, Nagoya, Aichi 4648601, Japan.
[Harashima, Nanae] Shimane Univ, Fac Med, Dept Immunol, Matsue, Shimane, Japan.
[Yokoyama, Hisayuki] Natl Hosp Org, Sendai Med Ctr, Dept Hematol, Sendai, Miyagi, Japan.
[Lerman, Michael I.] Affina Biotechnol Inc, Elmsford, NY 10523 USA.
RP Childs, RW (reprint author), NHLBI, NIH, 10 Ctr Dr 3E-5330, Bethesda, MD 20892 USA.
EM childsr@mail.nih.gov
FU NIH, National Heart, Lung, and Blood Institute, Hematology Branch
FX This work was supported by the intramural research program of NIH,
National Heart, Lung, and Blood Institute, Hematology Branch.
NR 24
TC 1
Z9 2
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2177
EP 2185
DI 10.1158/0008-5472.CAN-15-3139
PG 9
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700015
PM 26862115
ER
PT J
AU Farrar, JE
Schuback, HL
Ries, RE
Wai, D
Hampton, OA
Trevino, LR
Alonzo, TA
Auvil, JMG
Davidsen, TM
Gesuwan, P
Hermida, L
Muzny, DM
Dewal, N
Rustagi, N
Lewis, LR
Gamis, AS
Wheeler, DA
Smith, MA
Gerhard, DS
Meshinchi, S
AF Farrar, Jason E.
Schuback, Heather L.
Ries, Rhonda E.
Wai, Daniel
Hampton, Oliver A.
Trevino, Lisa R.
Alonzo, Todd A.
Auvil, Jaime M. Guidry
Davidsen, Tanja M.
Gesuwan, Patee
Hermida, Leandro
Muzny, Donna M.
Dewal, Ninad
Rustagi, Navin
Lewis, Lora R.
Gamis, Alan S.
Wheeler, David A.
Smith, Malcolm A.
Gerhard, Daniela S.
Meshinchi, Soheil
TI Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing
Mutational Landscape from Disease Diagnosis to Relapse
SO CANCER RESEARCH
LA English
DT Article
ID CHILDRENS-ONCOLOGY-GROUP; INTERNAL TANDEM DUPLICATION; SEQUENCING DATA;
MUTANT LEVEL; FLT3; IMPACT; AML; OUTCOMES; DNMT3A; TRIAL
AB The genomic and clinical information used to develop and implement therapeutic approaches for acute myelogenous leukemia (AML) originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COGTARGET-AML initiative used whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML. One hundred forty-five somatic variants at diagnosis (median 6 mutations/patient) and 149 variants at relapse (median 6.5 mutations) were identified and verified by orthogonal methodologies. Recurrent somatic variants [in (greater than or equal to) 2 patients] were identified for 10 genes (FLT3, NRAS, PTPN11, WT1, TET2, DHX15, DHX30, KIT, ETV6, KRAS), with variable persistence at relapse. The variant allele fraction (VAF), used to measure the prevalence of somatic mutations, varied widely at diagnosis. Mutations that persisted from diagnosis to relapse had a significantly higher diagnostic VAF compared with those that resolved at relapse (median VAF 0.43 vs. 0.24, P < 0.001). Further analysis revealed that 90% of the diagnostic variants with VAF > 0.4 persisted to relapse compared with 28% with VAF < 0.2 (P < 0.001). This study demonstrates significant variability in the mutational profile and clonal evolution of pediatric AML from diagnosis to relapse. Furthermore, mutations with high VAF at diagnosis, representing variants shared across a leukemic clonal structure, may constrain the genomic landscape at relapse and help to define key pathways for therapeutic targeting. (C) 2016 AACR.
C1 [Farrar, Jason E.] Arkansas Childrens Hosp, Res Inst, 800 Marshall St, Little Rock, AR 72202 USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Farrar, Jason E.; Alonzo, Todd A.; Meshinchi, Soheil] Childrens Oncol Grp, Monrovia, CA USA.
[Schuback, Heather L.; Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D5-380, Seattle, WA 98109 USA.
[Schuback, Heather L.; Ries, Rhonda E.; Meshinchi, Soheil] Univ Washington, Sch Med, Seattle, WA USA.
[Wai, Daniel] Phoenix Childrens Hosp, Ron Matricaria Inst Mol Med, Tucson, AZ USA.
[Wai, Daniel] Univ Arizona, Coll Med, Tucson, AZ USA.
[Hampton, Oliver A.; Trevino, Lisa R.; Muzny, Donna M.; Dewal, Ninad; Rustagi, Navin; Lewis, Lora R.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Trevino, Lisa R.] Doctors Hosp Renaissance, Edinburg, TX USA.
[Alonzo, Todd A.] Univ So Calif, Los Angeles, CA USA.
[Auvil, Jaime M. Guidry; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Davidsen, Tanja M.; Gesuwan, Patee; Hermida, Leandro] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Meshinchi, S (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D5-380, Seattle, WA 98109 USA.
EM smeshinc@fredhutch.org
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E, R01
CA114563, U10 CA098543, U10 CA180886, U10 CA180899]
NR 25
TC 8
Z9 8
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2197
EP 2205
DI 10.1158/0008-5472.CAN-15-1015
PG 9
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700017
PM 26941285
ER
PT J
AU Travis, RC
Appleby, PN
Martin, RM
Holly, JMP
Albanes, D
Black, A
Bueno-de-Mesquita, HB
Chan, JM
Chen, C
Chirlaque, MD
Cook, MB
Deschasaux, M
Donovan, JL
Ferrucci, L
Galan, P
Giles, GG
Giovannucci, EL
Gunter, MJ
Habel, LA
Hamdy, FC
Helzlsouer, KJ
Hercberg, S
Hoover, RN
Janssen, JAMJL
Kaaks, R
Kubo, T
Le Marchand, L
Metter, EJ
Mikami, K
Morris, JK
Neal, DE
Neuhouser, ML
Ozasa, K
Palli, D
Platz, EA
Pollak, MN
Price, AJ
Roobol, MJ
Schaefer, C
Schenk, JM
Severi, G
Stampfer, MJ
Stattin, P
Tamakoshi, A
Tangen, CM
Touvier, M
Wald, NJ
Weiss, NS
Ziegler, RG
Key, TJ
Allen, NE
AF Travis, Ruth C.
Appleby, Paul N.
Martin, Richard M.
Holly, Jeff M. P.
Albanes, Demetrius
Black, Amanda
Bueno-de-Mesquita, H. Bas
Chan, June M.
Chen, Chu
Chirlaque, Maria-Dolores
Cook, Michael B.
Deschasaux, Melanie
Donovan, Jenny L.
Ferrucci, Luigi
Galan, Pilar
Giles, Graham G.
Giovannucci, Edward L.
Gunter, Marc J.
Habel, Laurel A.
Hamdy, Freddie C.
Helzlsouer, Kathy J.
Hercberg, Serge
Hoover, Robert N.
Janssen, Joseph A. M. J. L.
Kaaks, Rudolf
Kubo, Tatsuhiko
Le Marchand, Loic
Metter, E. Jeffrey
Mikami, Kazuya
Morris, Joan K.
Neal, David E.
Neuhouser, Marian L.
Ozasa, Kotaro
Palli, Domenico
Platz, Elizabeth A.
Pollak, Michael N.
Price, Alison J.
Roobol, Monique J.
Schaefer, Catherine
Schenk, Jeannette M.
Severi, Gianluca
Stampfer, Meir J.
Stattin, Par
Tamakoshi, Akiko
Tangen, Catherine M.
Touvier, Mathilde
Wald, Nicholas J.
Weiss, Noel S.
Ziegler, Regina G.
Key, Timothy J.
Allen, Naomi E.
CA Endogenous Hormones Nutr
TI A Meta-analysis of Individual Participant Data Reveals an Association
between Circulating Levels of IGF-I and Prostate Cancer Risk
SO CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-2; FACTOR (IGF)-I;
SUSCEPTIBILITY LOCI; PREVENTION TRIAL; SERUM-INSULIN; FACTOR AXIS;
IGFBP-3; HYPERPLASIA; DIET
AB The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (P-trend all <= 0.005), and IGFBP-1 was inversely associated weakly with risk (P-trend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (P-heterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, P-heterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. (C) 2016 AACR.
C1 [Travis, Ruth C.; Appleby, Paul N.; Price, Alison J.; Key, Timothy J.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Martin, Richard M.; Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Martin, Richard M.] Univ Bristol, MRC, Univ Bristol Integrat Epidemiol Unit, Bristol, Avon, England.
[Martin, Richard M.] Natl Inst Hlth Res Bristol, Biomed Res Unit Nutr, Bristol, Avon, England.
[Holly, Jeff M. P.] Univ Bristol, Fac Med, Sch Clin Sci, Bristol, Avon, England.
[Albanes, Demetrius; Black, Amanda; Cook, Michael B.; Hoover, Robert N.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
[Bueno-de-Mesquita, H. Bas; Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
[Chen, Chu; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Chirlaque, Maria-Dolores] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.
[Chirlaque, Maria-Dolores] CIBER Epidemiol & Salud Publ, Madrid, Spain.
[Deschasaux, Melanie; Galan, Pilar; Hercberg, Serge; Touvier, Mathilde] Univ Paris 07, Univ Paris 05, Univ Paris 13,Inserm,U1153,INRA,U1125,Cnam, Sorbonne Paris Cite,Epidemiol & Biostat Res Ctr,N, F-93017 Bobigny, France.
[Ferrucci, Luigi; Metter, E. Jeffrey] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Med, 665 Huntington Ave, Boston, MA 02115 USA.
[Habel, Laurel A.; Schaefer, Catherine] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg, Oxford, England.
[Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Janssen, Joseph A. M. J. L.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Kubo, Tatsuhiko] Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 807, Japan.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Metter, E. Jeffrey] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
[Mikami, Kazuya] Kyoto Prefectural Univ Med, Kyoto, Japan.
[Morris, Joan K.; Wald, Nicholas J.] Queen Mary Univ London, Wolfson Inst Prevent Med, Charterhouse Sq, London, England.
[Neal, David E.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Ozasa, Kotaro] Radiat Effects Res Fdn, Hiroshima, Japan.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Pollak, Michael N.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Roobol, Monique J.] Erasmus MC, Dept Urol, Rotterdam, Netherlands.
[Schenk, Jeannette M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
[Schenk, Jeannette M.; Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Severi, Gianluca] Human Genet Fdn, Turin, Italy.
[Stampfer, Meir J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Stattin, Par] Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden.
[Tamakoshi, Akiko] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Tangen, Catherine M.] Univ Washington, Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98195 USA.
[Tangen, Catherine M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
RP Travis, RC (reprint author), Univ Oxford, Roosevelt Dr, Oxford OX3 7LF, England.
EM ruth.travis@ceu.ox.ac.uk
RI Cook, Michael/A-5641-2009;
OI Cook, Michael/0000-0002-0533-7302; Price, Alison/0000-0002-3891-3337;
PALLI, Domenico/0000-0002-5558-2437; Giles, Graham/0000-0003-4946-9099;
Kubo, Tatsuhiko/0000-0001-8822-9181
FU Cancer Research UK [A19169]; NCI NIH HHS [P01 CA108964, P01 CA033619,
P01 CA055075, R01 CA133891, R37 CA054281, U01 CA164973, U10 CA037429,
UG1 CA189974, UM1 CA182883]
NR 50
TC 6
Z9 6
U1 4
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2288
EP 2300
DI 10.1158/0008-5472.CAN-15-1551
PG 13
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700025
PM 26921328
ER
PT J
AU Shafer-Weaver, KA
Anderson, MJ
Draper, LJ
Malyguine, A
Alvord, WG
Greenberg, NM
Hurwitz, AA
AF Shafer-Weaver, Kimberly A.
Anderson, Michael J.
Draper, Lauren J.
Malyguine, Anatoli
Alvord, W. Gregory
Greenberg, Norman M.
Hurwitz, Arthur A.
TI Immunity to Murine Prostatic Tumors: Continuous Provision of T-Cell Help
Prevents CD8 T-Cell Tolerance and Activates Tumor-Infiltrating Dendritic
Cells (Retraction of vol 69, pg 6256, 2009)
SO CANCER RESEARCH
LA English
DT Correction
C1 [Shafer-Weaver, Kimberly A.; Anderson, Michael J.; Draper, Lauren J.; Hurwitz, Arthur A.] SAIC Frederick Inc, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program, Frederick, MD USA.
[Shafer-Weaver, Kimberly A.; Malyguine, Anatoli] SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD USA.
[Alvord, W. Gregory] NCI, Biostat Div, Data Management Serv, Frederick, MD 21701 USA.
[Greenberg, Norman M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
RP Shafer-Weaver, KA (reprint author), SAIC Frederick Inc, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program, Frederick, MD USA.; Shafer-Weaver, KA (reprint author), SAIC Frederick Inc, Lab Cell Mediated Immun, Frederick, MD USA.
NR 1
TC 0
Z9 0
U1 3
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2490
EP 2490
DI 10.1158/0008-5472.CAN-16-0505
PG 1
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700042
ER
PT J
AU Zhu, ZQ
Singh, V
Bronte, V
Shoe, JL
Feigenbaum, L
Hurwitz, AA
AF Zhu, Ziqiang
Singh, Vinod
Bronte, Vincenzo
Shoe, Jennifer L.
Feigenbaum, Lionel
Hurwitz, Arthur A.
TI High-Avidity T Cells Are Preferentially Tolerized in the Tumor
Microenvironment (Retraction of vol 73, pg 595, 2013)
SO CANCER RESEARCH
LA English
DT Correction
C1 [Zhu, Ziqiang; Singh, Vinod; Hurwitz, Arthur A.] Frederick Natl Lab Canc Res, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program, Frederick, MD USA.
[Bronte, Vincenzo] Univ Verona, Dept Pathol, I-37100 Verona, Italy.
[Shoe, Jennifer L.; Feigenbaum, Lionel] NCI, Lab Anim Sci Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Zhu, ZQ (reprint author), Frederick Natl Lab Canc Res, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program, Frederick, MD USA.
RI Bronte, Vincenzo/K-7902-2016
OI Bronte, Vincenzo/0000-0002-3741-5141
NR 1
TC 0
Z9 0
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2016
VL 76
IS 8
BP 2491
EP 2491
DI 10.1158/0008-5472.CAN-16-0506
PG 1
WC Oncology
SC Oncology
GA DJ4JH
UT WOS:000374170700043
ER
PT J
AU Thompson, KW
Joshi, P
Dymond, JS
Gorrepati, L
Smith, HE
Krause, MW
Eisenmann, DM
AF Thompson, Kenneth W.
Joshi, Pradeep
Dymond, Jessica S.
Gorrepati, Lakshmi
Smith, Harold E.
Krause, Michael W.
Eisenmann, David M.
TI The Paired-box protein PAX-3 regulates the choice between lateral and
ventral epidermal cell fates in C-elegans
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE C. elegans; Fate specification; Differentiation; Gene expression; PAX;
Epidermis
ID HEDGEHOG-RELATED GENES; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR;
PRISTIONCHUS-PACIFICUS; EMBRYONIC EPIDERMIS; EXPRESSION ANALYSIS;
HYPODERMAL CELLS; DIFFERENTIATION; MORPHOGENESIS; MUTATIONS
AB The development of the single cell layer skin or hypodermis of Caenorhabditis elegans is an excellent model for understanding cell fate specification and differentiation. Early in C. elegans embryogenesis, six rows of hypodermal cells adopt dorsal, lateral or ventral fates that go on to display distinct behaviors during larval life. Several transcription factors are known that function in specifying these major hypodermal cell fates, but our knowledge of the specification of these cell types is sparse, particularly in the case of the ventral hypodermal cells, which become Vulval Precursor Cells and form the vulval opening in response to extracellular signals. Previously, the gene pvl-4 was identified in a screen for mutants with defects in vulval development. We found by whole genome sequencing that pvl-4 is the Paired-box gene pax-3, which encodes the sole PAX-3 transcription factor homolog in C. elegans. pax-3 mutants show embryonic and larval lethality, and body morphology abnormalities indicative of hypodermal cell defects. We report that pax-3 is expressed in ventral P cells and their descendants during embryogenesis and early larval stages, and that in pax-3 reduction-of-function animals the ventral P cells undergo a cell fate transformation and express several markers of the lateral seam cell fate. Furthermore, forced expression of pax-3 in the lateral hypodermal cells causes them to lose expression of seam cell markers. We propose that pax-3 functions in the ventral hypodermal cells to prevent these cells from adopting the lateral seam cell fate. pax-3 represents the first gene required for specification solely of the ventral hypodermal fate in C elegans providing insights into cell type diversification. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Thompson, Kenneth W.; Joshi, Pradeep; Dymond, Jessica S.; Gorrepati, Lakshmi; Eisenmann, David M.] Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
[Smith, Harold E.; Krause, Michael W.] NIDDK, NIH, 5 Ctr Dr, Bethesda, MD 20892 USA.
[Thompson, Kenneth W.] Univ Florida, Dept Med, Div Hematol & Oncol, 1600 SW Archer Rd,POB 100278, Gainesville, FL 32610 USA.
[Joshi, Pradeep; Dymond, Jessica S.] Johns Hopkins Appl Phys Lab, 11100 Johns Hopkins Rd, Laurel, MD 20723 USA.
[Gorrepati, Lakshmi] Carnegie Inst Sci, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA.
RP Eisenmann, DM (reprint author), Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM Kenneth.Thompson@medicine.ufl.edu; pradeep.m.joshi@lifesci.ucsb.edu;
Jessica.Dymond@jhuapl.edu; gorrepati@ciwemb.edu; smithhe2@niddk.nih.gov;
michaelkr@niddk.nih.gov; eisenman@umbc.edu
OI Krause, Michael/0000-0001-6127-3940
FU NIH Office of Research Infrastructure Programs [P40 OD010440]; National
BioResource Project of Japan; National Science Foundation (NSF)
[IBN-0131485]; National Institute of Diabetes and Digestive and Kidney
Diseases; University of Maryland Baltimore County
FX We thank, A. Golden, I. Greenwald, I. Hamza, S. Kim, D. Miller and J.
Rothman for sharing reagents and strains and we thank Wormbase for as a
valuable resource of information. Some nematode and yeast strains used
in this work were provided by the Caenorhabditis Genetics Center that is
funded by the NIH Office of Research Infrastructure Programs (P40
OD010440), and by the National BioResource Project of Japan. This work
was supported by a National Science Foundation (NSF) grant IBN-0131485,
funding from The University of Maryland Baltimore County, and the
intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases.
NR 78
TC 0
Z9 0
U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD APR 15
PY 2016
VL 412
IS 2
BP 191
EP 207
DI 10.1016/j.ydbio.2016.03.002
PG 17
WC Developmental Biology
SC Developmental Biology
GA DJ4UW
UT WOS:000374204600002
PM 26953187
ER
PT J
AU Gustin, SE
Hogg, K
Stringer, JM
Rastetter, RH
Pelosi, E
Miles, DC
Sinclair, AH
Wilhelm, D
Western, PS
AF Gustin, Sonja E.
Hogg, Kirsten
Stringer, Jessica M.
Rastetter, Raphael H.
Pelosi, Emanuele
Miles, Denise C.
Sinclair, Andrew H.
Wilhelm, Dagmar
Western, Patrick S.
TI WNT/beta-catenin and p27/FOXL2 differentially regulate supporting cell
proliferation in the developing ovary
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE beta-catenin; WNT4; FOXL2; Ovary; Granulosa; Follicle
ID MAMMALIAN SEX DETERMINATION; TRANSCRIPTION FACTOR FOXL2; GERM-CELLS;
BETA-CATENIN; MOUSE OVARY; GENE-EXPRESSION; MITOTIC ARREST; STEM-CELLS;
MICE; WNT4
AB Sexual development is initiated through differentiation of testicular Sertoli cells or ovarian granulosa cells. Although these supporting cells are considered to develop from common bipotential precursors, recent evidence suggests that distinct supporting cell populations are present in the ovary, with one providing granulosa cells of the medullary follicles and the other providing granulosa cells of the cortical follicles, the latter of which support lifelong fertility. Here, we demonstrate that XX fetal gonads contain GATA4 expressing supporting cells that either enter mitotic arrest, or remain proliferative. Blocking WNT signalling reduces XX supporting cell proliferation, while stabilising beta-catenin signalling promotes proliferation, indicating that the renewal of pre-granulosa cells is dependent on WNT/beta-catenin signalling in the proliferative supporting cell population. In contrast, XX supporting cells express p27 and FOXL2 and are maintained in mitotic arrest. Although FOXL2 is required for maintaining high levels of p27 expression, it is dispensable for entry and maintenance of mitotic arrest in XX supporting cells. Combined our data suggest that both medullary and cortical precursors arise from a common GATA4 expressing cell type. In addition, this work indicates that a balance between supporting cell self-renewal and differentiation is maintained in the developing ovary by relative WNT/beta-catenin and p27/FOXL2 activities. This study provides significant new insights into the origin and formation of ovarian follicles and evidence supporting a common fetal origin of medullary and cortical granulosa cells. Crown Copyright (C) 2016 Published by Elsevier Inc. All rights reserved.
C1 [Gustin, Sonja E.; Hogg, Kirsten; Stringer, Jessica M.; Miles, Denise C.; Western, Patrick S.] Monash Univ, Hudson Inst Med Res, Ctr Genet Dis, Clayton, Vic, Australia.
[Gustin, Sonja E.; Hogg, Kirsten; Stringer, Jessica M.; Miles, Denise C.; Western, Patrick S.] Monash Univ, Dept Mol & Translat Sci, Clayton, Vic, Australia.
[Rastetter, Raphael H.; Wilhelm, Dagmar] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia.
[Pelosi, Emanuele] NIA, Genet Lab, NIH, IRP, Baltimore, MD 21224 USA.
[Sinclair, Andrew H.] Univ Melbourne, Dept Paediat, Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Gustin, Sonja E.; Miles, Denise C.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3050, Australia.
[Wilhelm, Dagmar] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3052, Australia.
RP Western, PS (reprint author), Hudson Inst Med Res, 27-31 Wright St, Clayton, Vic 3168, Australia.
EM patrick.western@hudson.org.au
RI Sinclair, Andrew/A-3598-2010; Wilhelm, Dagmar/B-6915-2009; Stringer,
Jessica/I-5525-2013
OI Sinclair, Andrew/0000-0003-2741-7992; Wilhelm,
Dagmar/0000-0002-7757-4075; Stringer, Jessica/0000-0003-4729-3026
FU Monash University Faculty of Medicine, Nursing and Health Sciences;
NHMRC [1043939, 1052195]; Victorian Government's Operational
Infrastructure Support Program, an NHMRC Program; Intramural Research
Program of the National Institute on Aging, NIH; ARC [FT110100327]
FX This work was supported by the Monash University Faculty of Medicine,
Nursing and Health Sciences and NHMRC Grant #1043939 to PW, the
Victorian Government's Operational Infrastructure Support Program, an
NHMRC Program grant awarded to AS and the Intramural Research Program of
the National Institute on Aging, NIH. DW is supported by an ARC Future
Fellowship (FT110100327). D.C.M. is supported by NHMRC Early Career
Fellowship (Grant #1052195).
NR 61
TC 3
Z9 3
U1 5
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD APR 15
PY 2016
VL 412
IS 2
BP 250
EP 260
DI 10.1016/j.ydbio.2016.02.024
PG 11
WC Developmental Biology
SC Developmental Biology
GA DJ4UW
UT WOS:000374204600006
PM 26939755
ER
PT J
AU Watts, M
Ha, J
Kimchi, O
Sherman, A
AF Watts, Margaret
Ha, Joon
Kimchi, Ofer
Sherman, Arthur
TI Paracrine regulation of glucagon secretion: the beta/alpha/delta model
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE insulin; pancreatic alpha-cell; glucagon; islet; somatostatin;
pancreatic delta-cell
ID PANCREATIC ALPHA-CELLS; INSULIN-SECRETION; BETA-CELLS; SOMATOSTATIN
RECEPTOR; ENDOCRINE PANCREAS; DELTA-CELLS; METABOLIC OSCILLATIONS;
GLUCOSE SUPPRESSION; POTASSIUM CHANNELS; PULSATILE INSULIN
AB The regulation of glucagon secretion in the pancreatic alpha-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the alpha-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic alpha-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (K-ATP) and a store-operated current (SOC). We have now developed an islet model that combines previously published mathematical models of alpha- and beta-cells with a new model of delta-cells and use it to explore the effects of insulin and somatostatin on glucagon secretion. We show that the model can reproduce experimental observations that the inhibitory effect of glucose remains even when paracrine modulators are no longer acting on the alpha-cell. We demonstrate how paracrine interactions can either synchronize alpha- nd delta-cells to produce pulsatile oscillations in glucagon and somatostatin secretion or fail to do so. The model can also account for the paradoxical observation that glucagon can be out of phase with insulin, whereas alpha-cell calcium is in phase with insulin. We conclude that both paracrine interactions and the alpha-cell's intrinsic mechanisms are needed to explain the response of glucagon secretion to glucose.
C1 [Watts, Margaret; Ha, Joon; Sherman, Arthur] NIH, Lab Biol Modeling, 12A South Dr,Rm 4007, Bethesda, MD 20892 USA.
[Kimchi, Ofer] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
RP Sherman, A (reprint author), NIH, Lab Biol Modeling, 12A South Dr,Rm 4007, Bethesda, MD 20892 USA.
EM ArthurS@niddk.nih.gov
FU Intramural Research Program of the National Institutes of Health
(National Institute of Diabetes and Digestive and Kidney Diseases)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Diabetes and
Digestive and Kidney Diseases).
NR 80
TC 0
Z9 0
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD APR 15
PY 2016
VL 310
IS 8
BP E597
EP E611
DI 10.1152/ajpendo.00415.2015
PG 15
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA DJ3IV
UT WOS:000374099100002
PM 26837808
ER
PT J
AU Bardou, O
Menou, A
Francois, C
Duitman, JW
von der Thusen, JH
Borie, R
Sales, KU
Mutze, K
Castier, Y
Sage, E
Liu, LG
Bugge, TH
Fairlie, DP
Konigshoff, M
Crestani, B
Borensztajn, KS
AF Bardou, Olivier
Menou, Awen
Francois, Charlene
Duitman, Jan Willem
von der Thusen, Jan H.
Borie, Raphael
Sales, Katiuchia Uzzun
Mutze, Kathrin
Castier, Yves
Sage, Edouard
Liu, Ligong
Bugge, Thomas H.
Fairlie, David P.
Koenigshoff, Melanie
Crestani, Bruno
Borensztajn, Keren S.
TI Membrane-anchored Serine Protease Matriptase Is a Trigger of Pulmonary
Fibrogenesis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE idiopathic pulmonary fibrosis; fibroblast; matriptase;
protease-activated receptor-2; camostat mesilate
ID PROTEINASE-ACTIVATED RECEPTOR-2; HEPATOCYTE GROWTH-FACTOR; PANCREATIC
FIBROSIS; INHIBITOR CAMOSTAT; LUNG FIBROSIS; FACTOR XA; TGF-BETA;
IN-VITRO; CELL; FIBROBLASTS
AB Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease that remains refractory to current therapies.
Objectives: To characterize the expression and activity of the membrane-anchored serine protease matriptase in IPF in humans and unravel its potential role in human and experimental pulmonary fibrogenesis.
Methods: Matriptase expression was assessed in tissue specimens from patients with IPF versus control subjects using quantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blotting, while matriptase activity was monitored by fluorogenic substrate cleavage. Matriptase-induced fibroproliferative responses and the receptor involved were characterized in human primary pulmonary fibroblasts by Western blot, viability, and migration assays. In the murine model of bleomycin-induced pulmonary fibrosis, the consequences of matriptase depletion, either by using the pharmacological inhibitor camostat mesilate (CM), or by genetic down-regulation using matriptase hypomorphic mice, were characterized by quantification of secreted collagen and immunostainings.
Measurements and Main Results: Matriptase expression and activity were up-regulated in IPF and bleomycin-induced pulmonary fibrosis. In cultured human pulmonary fibroblasts, matriptase expression was significantly induced by transforming growth factor-beta. Furthermore, matriptase elicited signaling via protease-activated receptor-2 (PAR-2), and promoted fibroblast activation, proliferation, and migration. In the experimental bleomycin model, matriptase depletion, by the pharmacological inhibitor CM or by genetic down-regulation, diminished lung injury, collagen production, and transforming growth factor-b expression and signaling.
Conclusions: These results implicate increased matriptase expression and activity in the pathogenesis of pulmonary fibrosis in human IPF and in an experimental mouse model. Overall, targeting matriptase, or treatment by CM, which is already in clinical use for other diseases, may represent potential therapies for IPF.
C1 [Bardou, Olivier; Menou, Awen; Francois, Charlene; Crestani, Bruno; Borensztajn, Keren S.] Med Sch Xavier Bichat, Inserm UMR1152, Paris, France.
[Bardou, Olivier; Menou, Awen; Francois, Charlene; Borie, Raphael; Crestani, Bruno; Borensztajn, Keren S.] Univ Paris Diderot, Sorbonne Paris Cite, Dept Hosp Univ FIRE Fibrosis Inflammat & Remodell, Paris, France.
[Bardou, Olivier; Menou, Awen; Francois, Charlene; Borie, Raphael; Crestani, Bruno; Borensztajn, Keren S.] LabEx Inflamex, Paris, France.
[Duitman, Jan Willem] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[von der Thusen, Jan H.] Dept Pathol, Erasmus Med Ctr, Rotterdam, Netherlands.
[Borie, Raphael; Crestani, Bruno] Bichat Claude Bernard Univ Hosp, AP HP, Dept Pulmonol A, Competence Ctr Rare Lung Dis, Paris, France.
[Sales, Katiuchia Uzzun; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Sales, Katiuchia Uzzun] Univ Sao Paulo Ribeirao Preto, Ribeirao Preto Sch Med, Dept Cell & Mol Biol, Sao Paulo, Brazil.
[Mutze, Kathrin; Koenigshoff, Melanie] Univ Munich, Helmholtz Zentrum Munchen, Univ Hosp, Comprehens Pneumol Ctr, Munich, Germany.
[Castier, Yves] Denis Diderot Univ, Bichat Claude Bernard Univ Hosp, AP HP, Dept Vasc & Thorac Surg, Paris, France.
[Castier, Yves] Med Sch Paris VII, Paris, France.
[Sage, Edouard] Hop Foch, Dept Thorac Surg & Lung Transplantat, Suresnes, France.
[Liu, Ligong; Fairlie, David P.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
RP Borensztajn, KS (reprint author), Univ Paris 07, INSERM UMR1152, 16 Rue Henri Huchard, F-75018 Paris, France.
EM keren.borensztajn@inserm.fr
RI liu, ligong/B-1690-2010;
OI liu, ligong/0000-0002-2693-1896; Borie, Raphael/0000-0002-9906-0024;
Fairlie, David/0000-0002-7856-8566
FU Fondation pour la Recherche Medicale [AJE201121]; Agence Nationale pour
la Recherche [ANR-14-CE15-0010-01]; Dutch Lung Foundation
[9.2.14.085FE]; Helmholtz Association; National Health and Medical
Research Council [1047759]; Senior Principal Research Fellowship
[1027369]; National Institute of Dental and Craniofacial Research
Intramural Research Program
FX Supported by grants from the Fondation pour la Recherche Medicale grant
AJE201121 (K.S.B.) and Agence Nationale pour la Recherche
ANR-14-CE15-0010-01 (O.B., A.M., and K.S.B.); Dutch Lung Foundation
grant 9.2.14.085FE (J.W.D.); the Helmholtz Association (K.M. and M.K.);
National Health and Medical Research Council grant 1047759 (L.L. and
D.P.F.); Senior Principal Research Fellowship 1027369 (D.P.F.); and the
National Institute of Dental and Craniofacial Research Intramural
Research Program (T.H.B. and K.U.S.).
NR 54
TC 4
Z9 4
U1 4
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD APR 15
PY 2016
VL 193
IS 8
BP 847
EP 860
DI 10.1164/rccm.201502-0299OC
PG 14
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DJ3NJ
UT WOS:000374112000013
PM 26599507
ER
PT J
AU Drilon, A
Eaton, AA
Schindler, K
Gounder, MM
Spriggs, DR
Harris, P
Ivy, SP
Iasonos, A
Lacouture, ME
Hyman, DM
AF Drilon, Alexander
Eaton, Anne A.
Schindler, Katja
Gounder, Mrinal M.
Spriggs, David R.
Harris, Pamela
Ivy, S. Percy
Iasonos, Alexia
Lacouture, Mario E.
Hyman, David M.
TI Beyond the dose-limiting toxicity period: Dermatologic adverse events of
patients on phase 1 trials of the Cancer Therapeutics Evaluation Program
SO CANCER
LA English
DT Article
DE Cancer Therapeutics Evaluation Program (CTEP); dermatologic toxicity;
dose-limiting toxicity (DLT) period; phase 1 trial; molecularly targeted
agents
ID MOLECULARLY TARGETED AGENTS; I ONCOLOGY TRIALS; THERAPIES; DESIGN;
IMPACT; GRADE
AB BACKGROUNDDermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date.
METHODSData from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized.
RESULTSIn total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade 3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P<.001) and differed by dose level (P<.001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P<.001).
CONCLUSIONSA substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities. Cancer 2016;122:1228-37. (c) 2016 American Cancer Society.
In 3517 patients with solid tumors who participate in Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials, a substantial proportion of drug-related dermatologic adverse events are observed after the traditional dose-limiting toxicity period. The cumulative incidence of these events is highest in patients who receive molecularly targeted agents, particularly combination kinase inhibitor-containing therapy.
C1 [Drilon, Alexander; Eaton, Anne A.; Gounder, Mrinal M.; Spriggs, David R.; Iasonos, Alexia; Lacouture, Mario E.; Hyman, David M.] Mem Sloan Kettering Canc Ctr, Dept Med, 300 East 66th St BAIC 1253, New York, NY 10065 USA.
[Drilon, Alexander; Gounder, Mrinal M.; Spriggs, David R.; Hyman, David M.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Schindler, Katja] Med Univ Vienna, Dept Dermatol, Vienna, Austria.
[Harris, Pamela; Ivy, S. Percy] NCI, Canc Therapeut & Evaluat Program, Bethesda, MD 20892 USA.
RP Drilon, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 300 East 66th St BAIC 1253, New York, NY 10065 USA.
EM drilona@mskcc.org
FU National Institutes of Health [P30 CA008748]
FX This work was funded in part by the cancer center core grant P30
CA008748 from the National Institutes of Health.
NR 27
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 15
PY 2016
VL 122
IS 8
BP 1228
EP 1237
DI 10.1002/cncr.29918
PG 10
WC Oncology
SC Oncology
GA DJ1IZ
UT WOS:000373957800014
PM 26916138
ER
PT J
AU Jansen, LA
Mahadevan, D
Appelbaum, PS
Klein, WMP
Weinstein, ND
Mori, M
Daffe, R
Sulmasy, DP
AF Jansen, Lynn A.
Mahadevan, Daruka
Appelbaum, Paul S.
Klein, William M. P.
Weinstein, Neil D.
Mori, Motomi
Daffe, Racky
Sulmasy, Daniel P.
TI Dispositional optimism and therapeutic expectations in early-phase
oncology trials
SO CANCER
LA English
DT Article
DE cancer research; dispositional optimism; informed consent; therapeutic
misconception; therapeutic optimism
ID CLINICAL-TRIALS; UNREALISTIC OPTIMISM; MISCONCEPTION; BENEFIT; HEALTH;
CONSENT; RISKS
AB BACKGROUNDPrior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism.
METHODSPatient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception.
RESULTSDispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception.
CONCLUSIONSHigh expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. Cancer 2016;122:1238-46. (c) 2016 American Cancer Society.
High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result only from misunderstanding. Data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations regarding specific aspects of trial participation.
C1 [Jansen, Lynn A.] Oregon Hlth & Sci Univ, Ctr Eth Hlth Care, Madeline Brill Nelson Chair Eth Educ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
[Mahadevan, Daruka] Univ Arizona, Ctr Canc, Med, Tucson, AZ USA.
[Appelbaum, Paul S.] Columbia Univ Coll Phys & Surg, Div Law Eth & Psychiat, 630 W 168th St, New York, NY 10032 USA.
[Klein, William M. P.] NCI, Behav Res Program, NIH, Bethesda, MD 20892 USA.
[Weinstein, Neil D.] Rutgers State Univ, Dept Human Ecol, New Brunswick, NJ 08903 USA.
[Mori, Motomi] Oregon Hlth & Sci Univ, Sch Publ Hlth & Med, Knight Canc Inst, Dept Canc Biostat, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
[Daffe, Racky] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Stat, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
[Sulmasy, Daniel P.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Sulmasy, Daniel P.] Univ Chicago, Divin Sch, Chicago, IL 60637 USA.
RP Jansen, LA (reprint author), Oregon Hlth & Sci Univ, Ctr Eth Hlth Care, Madeline Brill Nelson Chair Eth Educ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM jansen@ohsu.edu
FU National Institutes of Health/National Cancer [RO1CA166556];
Biostatistics Shared Resource of the Knight Cancer Institute (National
Cancer Institute) [5P30CA069533-16]
FX Supported by National Institutes of Health/National Cancer Institute
grant RO1CA166556. Biostatistics support (Motomi Mori and Racky Daffe)
was provided by the Biostatistics Shared Resource of the Knight Cancer
Institute (National Cancer Institute grant 5P30CA069533-16).
NR 24
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 15
PY 2016
VL 122
IS 8
BP 1238
EP 1246
DI 10.1002/cncr.29908
PG 9
WC Oncology
SC Oncology
GA DJ1IZ
UT WOS:000373957800015
PM 26882017
ER
PT J
AU Land, SR
Toll, BA
Moinpour, CM
Mitchell, SA
Ostroff, JS
Hatsukami, DK
Duffy, SA
Gritz, ER
Rigotti, NA
Brandon, TH
Prindiville, SA
Sarna, LP
Schnoll, RA
Herbst, RS
Cinciripini, PM
Leischow, SJ
Dresler, CM
Fiore, MC
Warren, GW
AF Land, Stephanie R.
Toll, Benjamin A.
Moinpour, Carol M.
Mitchell, Sandra A.
Ostroff, Jamie S.
Hatsukami, Dorothy K.
Duffy, Sonia A.
Gritz, Ellen R.
Rigotti, Nancy A.
Brandon, Thomas H.
Prindiville, Sheila A.
Sarna, Linda P.
Schnoll, Robert A.
Herbst, Roy S.
Cinciripini, Paul M.
Leischow, Scott J.
Dresler, Carolyn M.
Fiore, Michael C.
Warren, Graham W.
TI Research Priorities, Measures, and Recommendations for Assessment of
Tobacco Use in Clinical Cancer Research
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SELF-REPORTED SMOKING; RESEARCH POLICY STATEMENT; LUNG-CANCER; AMERICAN
ASSOCIATION; CESSATION SUPPORT; DIAGNOSIS; TRIALS; ONCOLOGY;
OPPORTUNITIES; ACCURACY
AB There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes "Core" items for minimal assessment of tobacco use at initial and follow-up time points, and an "Extension" set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. (C) 2016 AACR.
C1 [Land, Stephanie R.; Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA.
[Toll, Benjamin A.; Warren, Graham W.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Moinpour, Carol M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
[Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Hatsukami, Dorothy K.] Univ Minnesota DKH, Masonic Canc Ctr, Minneapolis, MN USA.
[Duffy, Sonia A.] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA.
[Duffy, Sonia A.] Ohio State Univ, HSR&D Ctr Excellence, VA Ctr Clin Management Res, Columbus, OH 43210 USA.
[Gritz, Ellen R.; Cinciripini, Paul M.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Brandon, Thomas H.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hlth Outcomes & Behav, Tampa, FL 33682 USA.
[Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Bethesda, MD 20892 USA.
[Sarna, Linda P.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
[Schnoll, Robert A.] Univ Penn, Philadelphia, PA 19104 USA.
[Herbst, Roy S.] Yale Univ, Sch Med, New Haven, CT USA.
[Leischow, Scott J.] Mayo Clin, Ctr Canc, Coll Med, Phoenix, AZ USA.
[Fiore, Michael C.] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Tobacco Res & Intervent, Madison, WI USA.
[Warren, Graham W.] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA.
[Warren, Graham W.] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA.
RP Land, SR (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM landsr@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA008748]
NR 53
TC 3
Z9 3
U1 4
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD APR 15
PY 2016
VL 22
IS 8
BP 1907
EP 1913
DI 10.1158/1078-0432.CCR-16-0104
PG 7
WC Oncology
SC Oncology
GA DJ3JP
UT WOS:000374101400011
PM 26888828
ER
PT J
AU Zorn, KK
Annunziata, CM
AF Zorn, Kristin K.
Annunziata, Christina M.
TI Editorial: Inhibiting PARP as a Strategic Target in Cancer
SO FRONTIERS IN ONCOLOGY
LA English
DT Editorial Material
DE PARP inhibitors; poly(ADP-ribose) polymerase; DNA repair; PARP-1; BRCA1
protein; cancer therapy
C1 [Zorn, Kristin K.] Univ Arkansas Med Sci, Dept Obstet & Gyencol, Little Rock, AR 72205 USA.
[Zorn, Kristin K.] Univ Arkansas Med Sci, Div Genet, Little Rock, AR 72205 USA.
[Annunziata, Christina M.] NCI, Bethesda, MD 20892 USA.
RP Zorn, KK (reprint author), Univ Arkansas Med Sci, Dept Obstet & Gyencol, Little Rock, AR 72205 USA.; Zorn, KK (reprint author), Univ Arkansas Med Sci, Div Genet, Little Rock, AR 72205 USA.
EM kkzorn@uams.edu
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD APR 15
PY 2016
VL 6
AR 91
DI 10.3389/fonc.2016.00091
PG 2
WC Oncology
SC Oncology
GA DJ4ZL
UT WOS:000374216500001
PM 27148483
ER
PT J
AU Du, VY
Bansal, A
Carlson, J
Salazar-Gonzalez, JF
Salazar, MG
Ladell, K
Gras, S
Josephs, TM
Heath, SL
Price, DA
Rossjohn, J
Hunter, E
Goepfert, PA
AF Du, Victor Y.
Bansal, Anju
Carlson, Jonathan
Salazar-Gonzalez, Jesus F.
Salazar, Maria G.
Ladell, Kristin
Gras, Stephanie
Josephs, Tracy M.
Heath, Sonya L.
Price, David A.
Rossjohn, Jamie
Hunter, Eric
Goepfert, Paul A.
TI HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute
Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EARLY HIV-1 INFECTION; IMMUNODEFICIENCY-VIRUS-INFECTION; CELLULAR
IMMUNE-RESPONSES; LYMPHOCYTE RESPONSES; ESCAPE MUTATIONS; TYPE-1
INFECTION; POPULATION-LEVEL; SIV INFECTION; VACCINE; EPITOPES
AB Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen.
C1 [Du, Victor Y.; Bansal, Anju; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Heath, Sonya L.; Goepfert, Paul A.] Univ Alabama Birmingham, Dept Med, 908 20th St South,CCB 330, Birmingham, AL 35294 USA.
[Carlson, Jonathan] Microsoft Res, Redmond, WA 98052 USA.
[Ladell, Kristin; Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Gras, Stephanie; Josephs, Tracy M.; Rossjohn, Jamie] Monash Univ, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3800, Australia.
[Gras, Stephanie; Josephs, Tracy M.; Rossjohn, Jamie] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Gras, Stephanie; Rossjohn, Jamie] Monash Univ, Australian Res Council, Ctr Excellence Adv Mol Imaging, Clayton, Vic 3800, Australia.
[Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA.
RP Goepfert, PA (reprint author), Univ Alabama Birmingham, Dept Med, 908 20th St South,CCB 330, Birmingham, AL 35294 USA.
EM paulg@uab.edu
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Salazar-Gonzalez,
Jesus/0000-0003-4626-6448; Ladell, Kristin/0000-0002-9856-2938; Carlson,
Jonathan/0000-0001-6618-3653; Heath , Sonya /0000-0002-3826-0954;
Rossjohn, Jamie/0000-0002-2020-7522
FU National Institutes of Health; Australian Research Council; National
Health and Medical Research Council of Australia; Wellcome Trust;
Australia Fellowship from the National Health and Medical Research
Council of Australia
FX This work was supported by the National Institutes of Health, the
Australian Research Council, the National Health and Medical Research
Council of Australia, and the Wellcome Trust. P.A.G. is supported by a
grant from the National Institutes of Health. S.G. is supported by an
Australian Research Council Future Fellowship. D.A.P. is supported by a
Wellcome Trust Senior Investigator Award. J.R. is supported by an
Australia Fellowship from the National Health and Medical Research
Council of Australia.
NR 75
TC 2
Z9 2
U1 1
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR 15
PY 2016
VL 196
IS 8
BP 3276
EP 3286
DI 10.4049/jimmunol.1502411
PG 11
WC Immunology
SC Immunology
GA DI8AA
UT WOS:000373721900007
PM 26983786
ER
PT J
AU Lee-Chang, C
Bodogai, M
Moritoh, K
Chen, X
Wersto, R
Sen, R
Young, HA
Croft, M
Ferrucci, L
Biragyn, A
AF Lee-Chang, Catalina
Bodogai, Monica
Moritoh, Kanako
Chen, Xin
Wersto, Robert
Sen, Ranjan
Young, Howard A.
Croft, Michael
Ferrucci, Luigi
Biragyn, Arya
TI Aging Converts Innate B1a Cells into Potent CD8(+) T Cell Inducers
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; AGE-RELATED-CHANGES; B-CELLS; IFN-GAMMA;
CLONAL EXPANSION; INTERFERON-GAMMA; DENDRITIC CELLS; 4-1BB LIGAND; B-1
CELLS; IN-VIVO
AB B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+) MHC class-I-Hi CD86(Hi) B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-gamma R1 on B1a cells to subsequently upregulate membrane TNF-alpha and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+) T cells by targeting TNFR2 via membrane TNF-alpha and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+) T cells.
C1 [Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Biragyn, Arya] NIA, Immunoregulat Sect, Baltimore, MD 21224 USA.
[Lee-Chang, Catalina] Lille Inflammat Res Int Ctr, INSERM UMR995, F-59000 Lille, France.
[Lee-Chang, Catalina] Univ Lille, F-59000 Lille, France.
[Chen, Xin] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Macao, Peoples R China.
[Chen, Xin; Young, Howard A.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Wersto, Robert] NIA, Flow Cytometry Unit, Baltimore, MD 21244 USA.
[Sen, Ranjan] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
[Croft, Michael] La Jolla Inst Allergy & Immunol, Div Immune Regulat, La Jolla, CA 92037 USA.
[Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
RP Biragyn, A (reprint author), NIA, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM biragyna@mail.nih.gov
RI Chen, Xin/I-6601-2015; Lee-Chang, Catalina/A-5580-2015;
OI Chen, Xin/0000-0002-2628-4027; Lee-Chang, Catalina/0000-0002-7675-2124;
Young, Howard/0000-0002-3118-5111
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 74
TC 1
Z9 1
U1 3
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR 15
PY 2016
VL 196
IS 8
BP 3385
EP 3397
DI 10.4049/jimmunol.1502034
PG 13
WC Immunology
SC Immunology
GA DI8AA
UT WOS:000373721900017
PM 26983789
ER
PT J
AU Shive, CL
Clagett, B
McCausland, MR
Mudd, JC
Funderburg, NT
Freeman, ML
Younes, SA
Ferrari, BM
Rodriguez, B
McComsey, GA
Calabrese, LH
Sieg, SF
Lederman, MM
AF Shive, Carey L.
Clagett, Brian
McCausland, Marie R.
Mudd, Joseph C.
Funderburg, Nicholas T.
Freeman, Michael L.
Younes, Souheil-Antoine
Ferrari, Brian M.
Rodriguez, Benigno
McComsey, Grace A.
Calabrese, Leonard H.
Sieg, Scott F.
Lederman, Michael M.
TI Inflammation Perturbs the IL-7 Axis, Promoting Senescence and Exhaustion
that Broadly Characterize Immune Failure in Treated HIV Infection
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE IL-6; senescence; immune failure; HIV; IL-1 beta; IL-7
ID T-CELL HOMEOSTASIS; ACTIVE ANTIRETROVIRAL THERAPY; GAMMA-CHAIN
CYTOKINES; PROGRAMMED DEATH-1; ACTIVATION; CD4; INTERLEUKIN-7;
EXPRESSION; DYSFUNCTION; RESPONSES
AB Background:
HIV-infected patients who fail to normalize CD4 T cells despite suppressive antiretroviral therapy have impaired immune homeostasis: diminished naive T-cell numbers, elevated T-cell turnover, senescence, and inflammation.
Methods:
Blood samples from immune failures (n = 60), immune successes (n = 20), and healthy controls (n = 20) were examined for plasma interleukin (IL)-7 levels, for cellular expression of the IL-7R alpha chain (CD127), for the exhaustion and senescence markers programed death 1 (PD-1) and CD57, and for the survival factor Bcl2. Because both inflammatory and homeostatic cytokines can induce T-cell cycling, we also examined the effects of these mediators on exhaustion and senescence markers.
Results:
Plasma levels of IL-7 were elevated and both CD4 and CD8 T-cell CD127 expression was decreased in immune failure. Plasma levels of IL-7 correlated directly with naive CD4 T-cell counts in immune success and inversely with T-cell cycling (Ki67) in healthy controls and immune success, but not in immune failure. CD4 T-cell density of PD-1 was increased and Bcl2+ CD4 T cells were decreased in immune failure but not in immune success, whereas the proportion of T cells expressing CD57 was increased in immune failure. PD-1 and CD57 were induced on CD4 but not CD8 T cells by stimulation in vitro with inflammatory IL-1 beta or homeostatic (IL-7) cytokines.
Conclusions:
Perturbation of the IL-7/IL-7 receptor axis, increased T-cell turnover, and increased senescence may reflect dysregulated responses to both homeostatic and inflammatory cytokines in immune failure patients.
C1 [Shive, Carey L.; Clagett, Brian; McCausland, Marie R.; Freeman, Michael L.; Younes, Souheil-Antoine; Ferrari, Brian M.; Rodriguez, Benigno; Sieg, Scott F.; Lederman, Michael M.] Case Western Reserve Univ, Dept Med, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA.
[Mudd, Joseph C.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Funderburg, Nicholas T.] Ohio State Univ, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA.
[Rodriguez, Benigno; McComsey, Grace A.; Lederman, Michael M.] Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Calabrese, Leonard H.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
RP Lederman, MM (reprint author), Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
EM lederman.michael@clevelandactu.org
RI Funderburg, Nicholas/L-8022-2013
FU National Institutes of Health [AI 076174, AI 68636, AI 105937]; CWRU
Center for AIDS Research [AI 36219]; Fasenmyer Foundation; National
Heart, Lung, And Blood Institute of the National Institutes of Health
[R00HL108743]
FX This work was supported by grants from the National Institutes of Health
(AI 076174, AI 68636, AI 105937) the CWRU Center for AIDS Research-(AI
36219) and the Fasenmyer Foundation. Research reported in this
publication was also supported by the National Heart, Lung, And Blood
Institute of the National Institutes of Health under Award Number
R00HL108743. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 54
TC 5
Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR 15
PY 2016
VL 71
IS 5
BP 483
EP 492
DI 10.1097/QAI.0000000000000913
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DG8RC
UT WOS:000372350300003
PM 26627102
ER
PT J
AU Bunge, KE
Dezzutti, CS
Rohan, LC
Hendrix, CW
Marzinke, MA
Richardson-Harman, N
Moncla, BJ
Devlin, B
Meyn, LA
Spiegel, HML
Hillier, SL
AF Bunge, Katherine E.
Dezzutti, Charlene S.
Rohan, Lisa C.
Hendrix, Craig W.
Marzinke, Mark A.
Richardson-Harman, Nicola
Moncla, Bernard J.
Devlin, Brid
Meyn, Leslie A.
Spiegel, Hans M. L.
Hillier, Sharon L.
TI A Phase 1 Trial to Assess the Safety, Acceptability, Pharmacokinetics,
and Pharmacodynamics of a Novel Dapivirine Vaginal Film
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV prevention; vaginal film; microbicide; dapivirine
ID HIV-NEGATIVE WOMEN; PREEXPOSURE PROPHYLAXIS; DOUBLE-BLIND; MICROBICIDE
GEL; AFRICAN WOMEN; PREVENTION; INFECTION; SPERMICIDES; HEALTHY;
QUANTIFICATION
AB Background:
Films may deliver antiretroviral drugs efficiently to mucosal tissues. In this first in-human trial of a vaginal film for delivering the nonnucleoside reverse transcriptase inhibitor dapivirine, safety, pharmacokinetics, and pharmacodynamics of film and gel formulations were compared with placebo.
Methods:
Sixty-one healthy HIV-negative women were randomized to daily dapivirine (0.05%) or placebo gel, or dapivirine (1.25 mg) or placebo film for seven days. The proportion of participants experiencing grade 2 and higher adverse events related to study product were compared. Plasma dapivirine concentrations were quantified. Paired cervical and vaginal tissue biopsies obtained similar to 2 hours after the last dose were measured for tissue drug concentration and exposed to HIV in an ex vivo challenge assay.
Results:
Two grade 2 related adverse events occurred in the placebo film group. Women randomized to gel and film products had 4 log(10) higher of dapivirine in cervical and vaginal tissues than plasma. Although gel and film users had comparable plasma dapivirine concentrations, tissue concentrations of dapivirine were 3-5 times higher in the gel users when compared with film users. HIV replication in the ex vivo challenge assay was significantly reduced in vaginal tissues from women randomized to dapivirine film or gel; furthermore, tissue drug concentrations were highly correlated with HIV protection. Women rated the film more comfortable with less leakage but found it more difficult to insert than gel.
Discussion:
Both film and gel delivered dapivirine at concentrations sufficient to block HIV ex vivo. This proof-of-concept study suggests film formulations for microbicides merit further investigation.
C1 [Bunge, Katherine E.; Dezzutti, Charlene S.; Moncla, Bernard J.; Hillier, Sharon L.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Dezzutti, Charlene S.; Rohan, Lisa C.; Moncla, Bernard J.; Meyn, Leslie A.; Hillier, Sharon L.] Magee Womens Res Inst, Pittsburgh, PA USA.
[Rohan, Lisa C.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA.
[Hendrix, Craig W.; Marzinke, Mark A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD 21205 USA.
[Richardson-Harman, Nicola] Alpha StatConsult, Damascus, MD USA.
[Devlin, Brid] Int Partnership Microbicides, Silver Spring, MD USA.
[Spiegel, Hans M. L.] HJF DAIDS, Rockville, MD USA.
[Spiegel, Hans M. L.] NIAID, NIH, US Dept HHS, Rockville, MD USA.
RP Bunge, KE (reprint author), Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, 300 Halket Ave, Pittsburgh, PA 15213 USA.
EM kbunge@mail.magee.edu
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [AI082639, UL1 TR000005]; National Institute of
Allergies and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services [HHSN272200800014C]
FX Supported by the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Grant AI082639 and UL1 TR000005. This
project has also been funded in part with federal funds from the
National Institute of Allergies and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
Contract No. HHSN272200800014C. The International Partnership for
Microbicides was the regulatory sponsor of the trial and donated
dapivirine drug substance for the films and the dapivirine gel used in
this study. The vaginal placebo gel was donated by CONRAD.
NR 30
TC 3
Z9 3
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR 15
PY 2016
VL 71
IS 5
BP 498
EP 505
DI 10.1097/QAI.0000000000000897
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DG8RC
UT WOS:000372350300005
PM 26565716
ER
PT J
AU Veronese, M
Zanotti-Fregonara, P
Rizzo, G
Bertoldo, A
Innis, RB
Turkheimer, FE
AF Veronese, Mattia
Zanotti-Fregonara, Paolo
Rizzo, Gaia
Bertoldo, Alessandra
Innis, Robert B.
Turkheimer, Federico E.
TI Measuring specific receptor binding of a PET radioligand in human brain
without pharmacological blockade: The genomic plot
SO NEUROIMAGE
LA English
DT Article
DE Non-displaceable binding; PET; Lassen plot; Allen brain atlas;
Pharmacological displacement; Pharmacological blockade; mRNA
ID POSITRON-EMISSION-TOMOGRAPHY; KAPPA-OPIOID RECEPTOR; PEPTIDE NOP
RECEPTORS; IN-VIVO; ANTAGONIST RADIOTRACER; REFERENCE REGION;
QUANTIFICATION; MODEL; PHOSPHODIESTERASE-4; C-11-LY2795050
AB PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions.
The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans.
In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade.
We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i.e. there were no significant posttranscriptional changes). This condition can be readily established a priori by assessing the correlation between PET and mRNA expression. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Veronese, Mattia; Turkheimer, Federico E.] Kings Coll London, Dept Neuroimaging, IoPPN, London SE5 8AF, England.
[Zanotti-Fregonara, Paolo; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Zanotti-Fregonara, Paolo] Univ Bordeaux, INCIA, CNRS, UMR 5287, Bordeaux, France.
[Rizzo, Gaia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy.
RP Turkheimer, FE (reprint author), Kings Coll London, Ctr Neuroimaging Sci, IoPPN, P089,De Crespigny Pk,Denmark Hill, London SE5 8AF, England.
EM federico.turkheimer@kcl.ac.uk
RI Turkheimer, Federico/B-9485-2012; Veronese, Mattia/A-6012-2013; Rizzo,
Gaia/A-8697-2013
OI Turkheimer, Federico/0000-0002-3766-3815; Veronese,
Mattia/0000-0003-3562-0683; Rizzo, Gaia/0000-0001-7272-8576
FU Programme Grant "Quantitative methodologies for Positron Emission
Tomography" (UK Medical Research Council) [G1100809/1]; Padova
University; National Institute of Mental Health (USA) [ZIAMH002852]
FX This study was supported by the Programme Grant "Quantitative
methodologies for Positron Emission Tomography" (UK Medical Research
Council No. G1100809/1), by the Padova University grant "Neuroimaging
Genetics: Models and Methods to Integrate Brain Phenotype and Genotype"
(2013), and by the Intramural Research Programme of the National
Institute of Mental Health (USA) project number ZIAMH002852 under
clinical trials.gov identifier NCT02230592.
NR 42
TC 0
Z9 0
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD APR 15
PY 2016
VL 130
BP 1
EP 12
DI 10.1016/j.neuroimage.2016.01.058
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DH4HG
UT WOS:000372745600001
PM 26850512
ER
PT J
AU Zhang, H
Japee, S
Nolan, R
Chu, C
Liu, N
Ungerleider, LG
AF Zhang, Hui
Japee, Shruti
Nolan, Rachel
Chu, Carlton
Liu, Ning
Ungerleider, Leslie G.
TI Face-selective regions differ in their ability to classify facial
expressions
SO NEUROIMAGE
LA English
DT Article
DE Amygdala; Emotional faces; fMRI; STS; SVM
ID SUPERIOR TEMPORAL SULCUS; HUMAN FUSIFORM GYRUS; HUMAN AMYGDALA;
EMOTIONAL EXPRESSIONS; NEURAL RESPONSES; FMRI-ADAPTATION; FUNCTIONAL
MRI; HUMAN BRAIN; IDENTITY; PERCEPTION
AB Recognition of facial expressions is crucial for effective social interactions. Yet, the extent to which the various face-selective regions in the human brain classify different facial expressions remains unclear. We used functional magnetic resonance imaging (fMRI) and support vector machine pattern classification analysis to determine how well face-selective brain regions are able to decode different categories of facial expression. Subjects participated in a slow event-related fMRI experiment in which they were shown 32 face pictures, portraying four different expressions: neutral, fearful, angry, and happy and belonging to eight different identities. Our results showed that only the amygdala and the posterior superior temporal sulcus (STS) were able to accurately discriminate between these expressions, albeit in different ways: the amygdala discriminated fearful faces from non-fearful faces, whereas STS discriminated neutral from emotional (fearful, angry and happy) faces. In contrast to these findings on the classification of emotional expression, only the fusiform face area (FFA) and anterior inferior temporal cortex (aIT) could discriminate among the various facial identities. Further, the amygdala and STS were better than FFA and aIT at classifying expression, while FFA and aIT were better than the amygdala and STS at classifying identity. Taken together, our findings indicate that the decoding of facial emotion and facial identity occurs in different neural substrates: the amygdala and STS for the former and FFA and aIT for the latter. Published by Elsevier Inc.
C1 [Zhang, Hui; Japee, Shruti; Nolan, Rachel; Chu, Carlton; Liu, Ning; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Zhang, H (reprint author), NIMH, Sect Neurocircuitry, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM hui.zhang@nih.gov
FU Intramural Research Program of the National Institute of Mental Health
[NCT01087281, 93-M-0170]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (NCT01087281; 93-M-0170).
NR 71
TC 1
Z9 1
U1 11
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD APR 15
PY 2016
VL 130
BP 77
EP 90
DI 10.1016/j.neuroimage.2016.01.045
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DH4HG
UT WOS:000372745600007
PM 26826513
ER
PT J
AU Dogo-Isonagie, C
Lee, SL
Lohith, K
Liu, HB
Mandadapu, SR
Lusvarghi, S
O'Connor, RD
Bewley, CA
AF Dogo-Isonagie, Cajetan
Lee, Su-Lin
Lohith, Katheryn
Liu, Hongbing
Mandadapu, Sivakoteswara R.
Lusvarghi, Sabrina
O'Connor, Robert D.
Bewley, Carole A.
TI Design and synthesis of small molecule-sulfotyrosine mimetics that
inhibit HIV-1 entry
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Tyrosine sulfate; Molecular docking; HIV co-receptors; CCR5 N-terminus;
Competitive inhibition
ID CCR5 N-TERMINUS; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; CO-RECEPTORS;
GP120; BINDING; CD4; DETERMINANTS; CORECEPTORS; ANTIBODIES
AB In the absence of a cure or vaccine for HIV/AIDS, small molecule inhibitors remain an attractive choice for antiviral therapeutics. Recent structural and functional studies of the HIV-1 surface envelope glycoprotein gp120 have revealed sites of vulnerability that can be targeted by small molecule and peptide inhibitors, thereby inhibiting HIV-1 infection. Here we describe a series of small molecule entry inhibitors that were designed to mimic the sulfated N-terminal peptide of the HIV-1 coreceptor CCR5. From a panel of hydrazonothiazolyl pyrazolinones, we demonstrate that compounds containing naphthyl di- and trisulfonic acids inhibit HIV-1 infection in single round infectivity assays with the disulfonic acids being the most potent. Molecular docking supports the observed structure activity relationship, and SPR confirmed binding to gp120. In infectivity assays treatment with a representative naphthyl disulfonate and a disulfated CCR5 N-terminus peptide results in competitive inhibition, with combination indices >2. In total this work shows that gp120 and HIV-1 infection can be inhibited by small molecules that mimic the function of, and are competitive with the natural sulfated CCR5 N-terminus. Published by Elsevier Ltd.
C1 [Dogo-Isonagie, Cajetan; Lee, Su-Lin; Lohith, Katheryn; Liu, Hongbing; Mandadapu, Sivakoteswara R.; Lusvarghi, Sabrina; O'Connor, Robert D.; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
FU NIH Intramural Research Program (NIDDK); Intramural AIDS Targeted
Antiviral Program, Office of the Director, NIH; NIH Intramural AIDS
Research Fellowship
FX This work was supported by the NIH Intramural Research Program (NIDDK)
and the Intramural AIDS Targeted Antiviral Program, Office of the
Director, NIH (C.A.B.). C.D.-I. acknowledges an NIH Intramural AIDS
Research Fellowship.
NR 34
TC 0
Z9 0
U1 7
U2 25
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD APR 15
PY 2016
VL 24
IS 8
BP 1718
EP 1728
DI 10.1016/j.bmc.2016.02.044
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA DH2CX
UT WOS:000372592900014
PM 26968647
ER
PT J
AU Yin, XY
Levy, D
Willinger, C
Adourian, A
Larson, MG
AF Yin, Xiaoyan
Levy, Daniel
Willinger, Christine
Adourian, Aram
Larson, Martin G.
TI Multiple imputation and analysis for high-dimensional incomplete
proteomics data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE multiple imputation; stepwise selection; high dimension; imputation
quality
ID ACUTE MYOCARDIAL-INFARCTION; PROTEIN; ANGIOGENESIS; ASSOCIATION;
ENDOSTATIN; DISEASE; GROWTH; MICE
AB Multivariable analysis of proteomics data using standard statistical models is hindered by the presence of incomplete data. We faced this issue in a nested case-control study of 135 incident cases of myocardial infarction and 135 pair-matched controls from the Framingham Heart Study Offspring cohort. Plasma protein markers (K=861) were measured on the case-control pairs (N=135), and the majority of proteins had missing expression values for a subset of samples. In the setting of many more variables than observations (K >> N), we explored and documented the feasibility of multiple imputation approaches along with subsequent analysis of the imputed data sets. Initially, we selected proteins with complete expression data (K=261) and randomly masked some values as the basis of simulation to tune the imputation and analysis process. We randomly shuffled proteins into several bins, performed multiple imputation within each bin, and followed up with stepwise selection using conditional logistic regression within each bin. This process was repeated hundreds of times. We determined the optimal method of multiple imputation, number of proteins per bin, and number of random shuffles using several performance statistics. We then applied this method to 544 proteins with incomplete expression data (40% missing values), from which we identified a panel of seven proteins that were jointly associated with myocardial infarction. (c) 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
C1 [Yin, Xiaoyan; Levy, Daniel; Willinger, Christine; Larson, Martin G.] NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
[Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Levy, Daniel; Willinger, Christine] NHLBI, Div Intramural Res, Populat Sci Branch, Boston, MA USA.
[Adourian, Aram] BG Med Inc, Waltham, MA USA.
[Yin, Xiaoyan] Boston Univ, Dept Cardiol, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Yin, XY (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM xyin@bu.edu
FU NIH [N01-HC-25195]; BG Medicine, Inc.; National Heart, Lung, and Blood
Institute; Boston University
FX This work is supported by NIH contract (N01-HC-25195) and Cooperative
Research and Development Agreement (CRADA) between BG Medicine, Inc.,
the National Heart, Lung, and Blood Institute, and Boston University.
NR 36
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD APR 15
PY 2016
VL 35
IS 8
BP 1315
EP 1326
DI 10.1002/sim.6800
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DF9LV
UT WOS:000371683600006
PM 26565662
ER
PT J
AU Kunzmann, AT
Coleman, HG
Huang, WY
Cantwell, MM
Kitahara, CM
Berndt, SI
AF Kunzmann, Andrew T.
Coleman, Helen G.
Huang, Wen-Yi
Cantwell, Marie M.
Kitahara, Cari M.
Berndt, Sonja I.
TI Fruit and vegetable intakes and risk of colorectal cancer and incident
and recurrent adenomas in the PLCO cancer screening trial
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE fruits; vegetables; colorectal cancer; colorectal adenoma; diet
ID PROSPECTIVE COHORT; DIETARY FIBER; RECTAL-CANCER; COLON-CANCER;
CONSUMPTION; HEALTH; METAANALYSIS; PREVENTION; NUTRITION; HABITS
AB The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio (3rd tertile) (vs.) (1st tertile)=0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) (3rd tertile) (vs.) (1st tertile)=0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR=0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.
What's new? It's not clear how much fruits and vegetables protect against colorectal cancer, or whether they impact the growth of adenoma, a precursor to colorectal cancer. To expand on existing data, these authors conducted a prospective study, in which all participants underwent the same screening protocol, eliminating a possible source of bias. They found that eating fruits and vegetables did not reduce the overall risk of developing adenoma, but did reduce the incidence of multiple adenomas. Particularly for those who consumed high amounts of processed meat, eating more fruits and vegetables helped reduce their risk of colorectal cancer.
C1 [Kunzmann, Andrew T.; Coleman, Helen G.; Cantwell, Marie M.] Queens Univ Belfast, Ctr Publ Hlth, Royal Victoria Hosp Site,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
[Huang, Wen-Yi; Kitahara, Cari M.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Kunzmann, AT (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Royal Victoria Hosp Site,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.; Kunzmann, AT (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci B, Royal Victoria Hosp Site,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM A.kunzmann@qub.ac.uk
RI Kitahara, Cari/R-8267-2016
FU Division of Cancer Epidemiology and Genetics (Intramural Research
Program); Division of Cancer Prevention, National Cancer Institute,
National Institutes of Health, United States Department of Health and
Human Services
FX Grant sponsors: Division of Cancer Epidemiology and Genetics (Intramural
Research Program) and by contracts from the Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health,
United States Department of Health and Human Services
NR 40
TC 3
Z9 3
U1 7
U2 50
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 15
PY 2016
VL 138
IS 8
BP 1851
EP 1861
DI 10.1002/ijc.29922
PG 11
WC Oncology
SC Oncology
GA DD7CU
UT WOS:000370082100006
PM 26559156
ER
PT J
AU Linet, MS
Brown, LM
Mbulaiteye, SM
Check, D
Ostroumova, E
Landgren, A
Devesa, SS
AF Linet, Martha S.
Brown, Linda M.
Mbulaiteye, Sam M.
Check, David
Ostroumova, Evgenia
Landgren, Annelie
Devesa, Susan S.
TI International long-term trends and recent patterns in the incidence of
leukemias and lymphomas among children and adolescents ages 0-19 years
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE childhood; incidence; trends; Hodgkin lymphoma; lymphoid leukemia;
myeloid leukemia; non-Hodgkin lymphoma
ID INFORMATION-SYSTEM PROJECT; CHILDHOOD-CANCER INCIDENCE; ACUTE
LYMPHOBLASTIC-LEUKEMIA; EUROPEAN CHILDREN; HODGKINS-DISEASE;
UNITED-STATES; MORTALITY-RATES; TEMPORAL TRENDS; TIME TRENDS; SURVIVAL
AB To enhance understanding of etiology, we examined international population-based cancer incidence data for lymphoid leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma and myeloid leukemia among children aged 0-19. Based on temporal trends during 1978-2007 in 24 populations, lymphoid leukemia and myeloid leukemia incidence rates generally have not changed greatly and differences in rates for non-Hodgkin and for Hodgkin lymphoma have diminished in some regions. Lymphoid leukemia rates during 2003-2007 in 54 populations varied about 10-fold, with rates highest in US white Hispanics (50.2 per million person-years) and Ecuador (48.3) and lowest in US blacks (20.4), Tunisia (17.7) and Uganda (6.9). Non-Hodgkin lymphoma rates varied 30-fold, with very high rates in sub-Saharan Africa (146.0 in Malawi and 54.3 in Uganda) and low rates (10) in some Asian populations (China, Japan, India, the Philippines and Thailand) and U.S. Asian-Pacific Islanders, eastern and northern European populations and Puerto Rico. Hodgkin lymphoma rates varied 15-fold, with rates highest in Italy (21.3) and lowest in China (1.7) . Myeloid leukemia rates varied only about fivefold, with rates highest in the Philippines and Korea (exceeding 14.0) and lowest in Eastern Europe (5.9 in Serbia and 5.3 in the Czech Republic) and Uganda (2.7). The boy/girl average incidence rate ratios were 2.00 or lower. Age-specific patterns differed among the four hematopoietic malignancies, but were generally consistent within major categories world-wide, except for non-Hodgkin lymphoma. A systematic world-wide approach comparing postulated etiologic factors in low- versus high-risk populations may help clarify the etiology of these childhood malignancies.
What's new? This first study to assess systematically long-term (1978-2007) incidence trends for childhood leukemias and lymphomas across five continents found that lymphoid and myeloid leukemia rates generally have not changed greatly, while regional differences in non-Hodgkin and Hodgkin lymphoma rates have diminished over time. During 2003-2007 age-adjusted incidence rates spanning five continents for non-Hodgkin lymphoma have varied 30-fold, Hodgkin lymphoma 15-fold, lymphoid leukemia 10-fold, and myeloid leukemia only 5-fold.
C1 [Linet, Martha S.; Mbulaiteye, Sam M.; Check, David; Ostroumova, Evgenia; Landgren, Annelie; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA.
[Brown, Linda M.] RTI Int, Rockville, MD USA.
RP Linet, MS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA.; Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA.
EM linetm@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; U.S. Public Health Service of the Department
of Health and Human Services
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health, National Cancer Institute, and the U.S. Public Health Service of
the Department of Health and Human Services.
NR 50
TC 7
Z9 7
U1 3
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 15
PY 2016
VL 138
IS 8
BP 1862
EP 1874
DI 10.1002/ijc.29924
PG 13
WC Oncology
SC Oncology
GA DD7CU
UT WOS:000370082100007
PM 26562742
ER
PT J
AU Stang, A
Kowall, B
Rusner, C
Trabert, B
Bray, F
Schuz, J
McGlynn, KA
Kuss, O
AF Stang, Andreas
Kowall, Bernd
Rusner, Carsten
Trabert, Britton
Bray, Freddie
Schuez, Joachim
McGlynn, Katherine A.
Kuss, Oliver
TI A novel method for identifying settings for well-motivated ecologic
studies of cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE neoplasms; etiology; cancer registries; incidence
ID AGGREGATE DATA; THYROID-CANCER; RECENT TRENDS; DISEASE RISK; MORTALITY;
EPIDEMIOLOGY; PREVENTION; SURVIVAL; PATTERNS; EUROPE
AB A low within-country variability and a large between-country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within- and between-country variability of cancer incidence to motivate high-quality ecologic studies. We extracted age-standardized incidence rate estimates (world standard population) from 135 regions for the ten most frequent invasive cancers in Europe for non-Hispanic white populations from Cancer Incidence in Five Continents, Volume X. We fitted weighted multilevel Poisson regression models with random country effects for each cancer and sex. We estimated intraclass correlation coefficients (ICCs) and 95% confidence intervals (95% CIs). A high ICC indicates a low within- and a high between-country variability of rates. The two cancer sites with the highest ICC among men were prostate cancer (0.96, 95% CI: 0.92-0.99) and skin melanoma (0.78, 0.64-0.93). Among women, high ICCs were observed for lung cancer (0.84, 0.73-0.95) and breast cancer (0.80, 0.69-0.91). The two most prominent sex differences for ICC occurred for cancers of the head and neck (men: 0.70, 0.55-0.85, women: 0.19, 0.08-0.30) and breast cancer (men: 0.04, 0.01-0.07, women: 0.80, 0.69-0.91). ICCs were relatively low for pancreatic cancer (men: 0.23, 0.10-0.35; women: 0.13, 0.04-0.21) and leukemia (men: 0.12, 0.04-0.21; women: 0.08, 0.02-0.14). For cancers with high ICC for which systematic factors of the health care system, screening and diagnostic activities are not plausible explanations for between-country variations in incidence, cross-country sex-specific ecologic studies may be especially promising.
What's new? For many cancer types, variations in incidence are larger between countries than they are within countries. Such differences suggest that population-level, or ecologic, factors significantly influence the incidence of certain malignancies. Here, incidence rate estimates for 10 invasive cancers were compared across 135 non-Hispanic white populations in countries in Europe and North America. Cancers with high intraclass correlation (ICC) values, indicating low within-country and high between-country variation, included prostate cancer and skin melanoma. Sex-specific variations in ICC were also identified. The methodology employed here could form the basis for in-depth analyses of geographical variations in cancer incidence.
C1 [Stang, Andreas; Kowall, Bernd] Univ Hosp Essen, Ctr Clin Epidemiol, Inst Med Informat Biometry & Epidemiol, Hufelandstr 55, D-45147 Essen, Germany.
[Stang, Andreas] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Stang, Andreas] German Consortium Translat Canc Res DKTK, Heidelberg, Germany.
[Rusner, Carsten] Univ Halle Wittenberg, Fac Med, Inst Med Epidemiol Biometry & Informat, D-06108 Halle, Germany.
[Trabert, Britton; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Bray, Freddie] Int Agcy Res Canc, Sect Canc Surveillance, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Schuez, Joachim] Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Kuss, Oliver] Univ Dusseldorf, Fac Med, Ctr Hlth & Soc, Dusseldorf, Germany.
[Kuss, Oliver] Univ Dusseldorf, German Diabet Ctr, Leibniz Inst Diabet Res, Inst Epidemiol & Biometry, Dusseldorf, Germany.
RP Stang, A (reprint author), Univ Hosp Essen, Ctr Clin Epidemiol, Inst Med Informat Biometry & Epidemiol, Hufelandstr 55, D-45147 Essen, Germany.; Stang, A (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.; Stang, A (reprint author), German Consortium Translat Canc Res DKTK, Heidelberg, Germany.
EM andreas.stang@uk-halle.de
RI Trabert, Britton/F-8051-2015;
OI Kuss, Oliver/0000-0003-3301-5869
FU German Federal Ministry of Education and Science (BMBF) [01ER1305]
FX Grant sponsor: German Federal Ministry of Education and Science (BMBF);
Grant number: 01ER1305
NR 27
TC 0
Z9 0
U1 2
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 15
PY 2016
VL 138
IS 8
BP 1887
EP 1893
DI 10.1002/ijc.29931
PG 7
WC Oncology
SC Oncology
GA DD7CU
UT WOS:000370082100009
PM 26595447
ER
PT J
AU McCann, KL
Teramoto, T
Zhang, J
Hall, TMT
Baserga, SJ
AF McCann, Kathleen L.
Teramoto, Takamasa
Zhang, Jun
Hall, Traci M. Tanaka
Baserga, Susan J.
TI The molecular basis for ANE syndrome revealed by the large ribosomal
subunit processome interactome
SO ELIFE
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTION; RNA RECOGNITION MOTIFS; EXON JUNCTION
COMPLEX; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; YEAST; BIOGENESIS;
EXPRESSION; COMPONENT; BINDING
AB ANE syndrome is a ribosomopathy caused by a mutation in an RNA recognition motif of RBM28, a nucleolar protein conserved to yeast (Nop4). While patients with ANE syndrome have fewer mature ribosomes, it is unclear how this mutation disrupts ribosome assembly. Here we use yeast as a model system and show that the mutation confers growth and pre-rRNA processing defects. Recently, we found that Nop4 is a hub protein in the nucleolar large subunit (LSU) processome interactome. Here we demonstrate that the ANE syndrome mutation disrupts Nop4's hub function by abrogating several of Nop4's protein-protein interactions. Circular dichroism and NMR demonstrate that the ANE syndrome mutation in RRM3 of human RBM28 disrupts domain folding. We conclude that the ANE syndrome mutation generates defective protein folding which abrogates protein-protein interactions and causes faulty pre-LSU rRNA processing, thus revealing one aspect of the molecular basis of this human disease.
C1 [McCann, Kathleen L.; Baserga, Susan J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Teramoto, Takamasa; Zhang, Jun; Hall, Traci M. Tanaka] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Baserga, Susan J.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA.
[Baserga, Susan J.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA.
RP Baserga, SJ (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.; Hall, TMT (reprint author), NIEHS, Epigenet & Stem Cell Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Baserga, SJ (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA.; Baserga, SJ (reprint author), Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA.
EM hall4@niehs.nih.gov; susan.baserga@yale.edu
RI Zhang, Jun/R-1502-2016
OI Zhang, Jun/0000-0002-5842-7424
FU National Institute of Environmental Health Sciences [1ZIAES050165];
National Institute of General Medical Sciences [0115710]; National
Institutes of Health [T32 GM 007499]
FX National Institute of Environmental Health Sciences 1ZIAES050165
Takamasa Teramoto Jun Zhang Traci M Tanaka Hall; National Institute of
General Medical Sciences 0115710 Kathleen L McCann Susan J Baserga;
National Institutes of Health T32 GM 007499 Kathleen McCann; The funders
had no role in study design, data collection and interpretation, or the
decision to submit the work for publication.
NR 38
TC 1
Z9 1
U1 1
U2 1
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD APR 14
PY 2016
VL 5
AR e16381
DI 10.7554/eLife.16381
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DM3PX
UT WOS:000376259600001
ER
PT J
AU Zhu, YZ
Ma, BY
Qe, RX
Nussinov, R
Zhang, QW
AF Zhu, Yuzhen
Ma, Buyong
Qe, Ruxi
Nussinov, Ruth
Zhang, Qingwen
TI Temperature-Dependent Conformational Properties of Human Neuronal
Calcium Sensor-1 Protein Revealed by All-Atom Simulations
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID BURIED SALT BRIDGES; MOLECULAR-DYNAMICS; BINDING PROPERTIES;
AMYLOID-BETA; WATER MODELS; C. ELEGANS; STABILITY; FREQUENIN; NETWORKS;
NCS-1
AB Neuronal calcium sensor-1 (NCS-1) protein has orthologues from Saccharomyces cerevisiae to human with highly conserved amino acid sequences. NCS-1 is an important factor controlling the animal's response to temperature change. This leads us to investigate the temperature effects on the conformational dynamics of human NCS-1 at 310 and 316 K by all-atom molecular dynamics (MD) simulations and dynamic community network analysis. Four independent 500 ns MD simulations show that secondary structure content at 316 K is similar to that at 310 K, whereas the global protein structure is expanded. Loop 3 (L3) adopts an extended state occuping the hydrophobic crevice, and the number of suboptimal communication paths between residue D176 and V190 is reduced at 316 K. The dynamic community network analysis suggests that the interdomain correlation is weakened, and the intradomain coupling is strengthened at 316 K. The elevated temperature reduces the number of the salt bridges, especially in C-domain. This study suggests that the elevated temperature affects the conformational dynamics of human NCS-1 protein. Comparison of the structural dynamics of R102Q mutant and Delta 176-190 truncated NCS-1 suggests that the structural and dynamical response of NCS-1 protein to elevated temperature may be one of its intrinsic functional properties.
C1 [Zhu, Yuzhen; Zhang, Qingwen] Shanghai Univ Sport, Coll Phys Educ & Training, 399 Chang Hai Rd, Shanghai 200438, Peoples R China.
[Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Qe, Ruxi] Fudan Univ, Dept Phys, 220 Handan Rd, Shanghai 200433, Peoples R China.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Zhang, QW (reprint author), Shanghai Univ Sport, Coll Phys Educ & Training, 399 Chang Hai Rd, Shanghai 200438, Peoples R China.
EM zgw@sus.edu.cn
RI Ma, Buyong/F-9491-2011;
OI Ma, Buyong/0000-0002-7383-719X; Zhang, Qingwen/0000-0002-8885-1066
FU Graduate Student Education Innovation Plan of Shanghai University of
Sports [yjscx2015003]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for
Cancer Research
FX This project has been funded from Graduate Student Education Innovation
Plan of Shanghai University of Sports (Grant yjscx2015003). Simulations
were performed at the High Performance Computing Server (PowerEdge T710)
of Shanghai University of Sport. This project has been funded in whole
or in part with Federal funds from the National Cancer Institute,
National Institutes of Health, under Contract HHSN261200800001E. This
research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
TC 1
Z9 1
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD APR 14
PY 2016
VL 120
IS 14
BP 3551
EP 3559
DI 10.1021/acs.jpcb.5b12299
PG 9
WC Chemistry, Physical
SC Chemistry
GA DJ7ZF
UT WOS:000374431000010
PM 27007011
ER
PT J
AU Aprelikova, O
Chen, K
El Touny, LH
Brignatz-Guittard, C
Han, J
Qiu, TH
Yang, HH
Lee, MP
Zhu, M
Green, JE
AF Aprelikova, Olga
Chen, Kenny
El Touny, Lara H.
Brignatz-Guittard, Constance
Han, Justin
Qiu, Tinghu
Yang, Howard H.
Lee, Maxwell P.
Zhu, Min
Green, Jeffrey E.
TI The epigenetic modifier JMJD6 is amplified in mammary tumors and
cooperates with c-Myc to enhance cellular transformation, tumor
progression, and metastasis
SO CLINICAL EPIGENETICS
LA English
DT Article
DE Mammary cancer; Myc; JMJD6; Copy number variants; Epigenetics; Tumor
progression
ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN BREAST-CANCER; TRANSCRIPTIONAL
PAUSE RELEASE; TAG TRANSGENIC MICE; PROTEIN 6 JMJD6; VEGF-RECEPTOR 1;
GENE-EXPRESSION; ARGININE METHYLATION; INDUCED APOPTOSIS; KI-RAS
AB Background: Oncogene overexpression in primary cells often triggers the induction of a cellular safeguard response promoting senescence or apoptosis. Secondary cooperating genetic events are generally required for oncogene-induced tumorigenesis to overcome these biologic obstacles. We employed comparative genomic hybridization for eight genetically engineered mouse models of mammary cancer to identify loci that might harbor genes that enhance oncogene-induced tumorigenesis.
Results: Unlike many other mammary tumor models, the MMTV-Myc tumors displayed few copy number variants except for amplification of distal mouse chromosome 11 in 80 % of the tumors (syntenic to human 17q23-qter often amplified in human breast cancer). Analyses of candidate genes located in this region identified JMJD6 as an epigenetic regulatory gene that cooperates with Myc to enhance tumorigenesis. It suppresses Myc-induced apoptosis under varying stress conditions through inhibition of p19ARF messenger RNA (mRNA) and protein, leading to reduced levels of p53. JMJD6 binds to the p19ARF promoter and exerts its inhibitory function through demethylation of H4R3me2a. JMJD6 overexpression in MMTV-Myc cell lines increases tumor burden, induces EMT, and greatly enhances tumor metastasis. Importantly, we demonstrate that co-expression of high levels of JMJD6 and Myc is associated with poor prognosis for human ER+ breast cancer patients.
Conclusions: A novel epigenetic mechanism has been identified for how JMJD6 cooperates with Myc during oncogenic transformation. Combined high expression of Myc and JMJD6 confers a more aggressive phenotype in mouse and human tumors. Given the pleiotropic pro-tumorigenic activities of JMJD6, it may be useful as a prognostic factor and a therapeutic target for Myc-driven mammary tumorigenesis.
C1 [Aprelikova, Olga; Chen, Kenny; El Touny, Lara H.; Brignatz-Guittard, Constance; Han, Justin; Qiu, Tinghu; Yang, Howard H.; Lee, Maxwell P.; Zhu, Min; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
RP Aprelikova, O (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
EM apreliko@mail.nih.gov
OI Chen, Kenny/0000-0002-1939-9213
FU Intramural Research Program of the NIH; CCR; NCI
FX This work was supported by the Intramural Research Program of the NIH,
CCR, and NCI. We would like to thank Dr. Evan and Dr. Lazebnik for
pBabe-MycER (TM) puro and hygro plasmids, Dr. Desai for pLV-JMJD6 and
LacZ plasmids, Dr. Johnson for pBabe-p19ARF plasmid, Dr. Liu for
depositing data into Gene Expression Omnibus, and members of Green lab
for helpful discussions. We are grateful to Dr. Kent Hunter for critical
reading of the manuscript. We would also like to thank the Array Core
Facility of the National Cancer Institute for performing array CGH
analysis.
NR 69
TC 1
Z9 1
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1868-7083
J9 CLIN EPIGENETICS
JI Clin. Epigenetics
PD APR 14
PY 2016
VL 8
AR 38
DI 10.1186/s13148-016-0205-6
PG 16
WC Oncology
SC Oncology
GA DK1KW
UT WOS:000374672100001
PM 27081402
ER
PT J
AU Peng, C
Yao, G
Gao, BM
Fan, CX
Bian, C
Wang, JT
Cao, Y
Wen, B
Zhu, YB
Ruan, ZQ
Zhao, XF
You, XX
Bai, J
Li, J
Lin, ZL
Zou, SJ
Zhang, XH
Qiu, Y
Chen, JM
Coon, SL
Yang, JA
Chen, JS
Shi, Q
AF Peng, Chao
Yao, Ge
Gao, Bing-Miao
Fan, Chong-Xu
Bian, Chao
Wang, Jintu
Cao, Ying
Wen, Bo
Zhu, Yabing
Ruan, Zhiqiang
Zhao, Xiaofei
You, Xinxin
Bai, Jie
Li, Jia
Lin, Zhilong
Zou, Shijie
Zhang, Xinhui
Qiu, Ying
Chen, Jieming
Coon, Steven L.
Yang, Jiaan
Chen, Ji-Sheng
Shi, Qiong
TI High-throughput identification of novel conotoxins from the Chinese
tubular cone snail (Conus betulinus) by multi-transcriptome sequencing
SO GIGASCIENCE
LA English
DT Article
DE Cone snail; Conopeptide; Conotoxin; Conus betulinus; Transcriptome;
Venom duct; Venom bulb
ID VENOM-DUCT TRANSCRIPTOME; ION-CHANNEL; RNA-SEQ; INTRASPECIFIC VARIATION;
PEPTIDE THERAPEUTICS; MOLECULAR PHYLOGENY; ALPHA-CONOTOXIN; TOXIN
DIVERSITY; PREY CAPTURE; CHRONIC PAIN
AB Background: The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species.
Results: The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels.
Conclusions: We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.
C1 [Peng, Chao; Bian, Chao; Wang, Jintu; Wen, Bo; Zhu, Yabing; Ruan, Zhiqiang; You, Xinxin; Bai, Jie; Li, Jia; Lin, Zhilong; Zou, Shijie; Zhang, Xinhui; Qiu, Ying; Chen, Jieming; Shi, Qiong] BGI Shenzhen, Shenzhen 518083, Peoples R China.
[Yao, Ge; Fan, Chong-Xu; Cao, Ying; Chen, Ji-Sheng] Res Inst Pharmaceut Chem, Beijing 102205, Peoples R China.
[Gao, Bing-Miao] Hainan Med Univ, Sch Pharmaceut Sci, Haikou 571199, Peoples R China.
[Bian, Chao; Ruan, Zhiqiang; You, Xinxin; Bai, Jie; Li, Jia; Zhang, Xinhui; Qiu, Ying; Chen, Jieming; Shi, Qiong] Shenzhen Key Lab Marine Genom, Guangdong Prov Key Lab Mol Breeding Marine Econ A, State Key Lab Agr Genom, Shenzhen 518083, Peoples R China.
[Zhao, Xiaofei; Yang, Jiaan] Micro Pharmatech Ltd, Wuhan 430075, Peoples R China.
[Coon, Steven L.] NIH, Mol Genom Lab, Bldg 10, Bethesda, MD 20892 USA.
[Shi, Qiong] BGI Zhenjiang Inst Hydrobiol, Zhenjiang 212000, Peoples R China.
RP Shi, Q (reprint author), BGI Shenzhen, Shenzhen 518083, Peoples R China.; Chen, JS (reprint author), Res Inst Pharmaceut Chem, Beijing 102205, Peoples R China.
EM chenjsh@cae.cn; shiqiong@genomics.cn
FU China 863 Program [2014AA093501]; Shenzhen Dapeng Special Program for
Industrial Development [KY20150207]; Special Project on the Integration
of Industry, Education and Research of Guangdong Province
[2013B090800017]; Shenzhen Scientific RD Program [CXB201108250095A];
State Key Laboratory of Agricultural Genomics [ZDSY20120618171817275];
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development at the National
Institutes of Health, USA
FX This work was supported by China 863 Program (No. 2014AA093501),
Shenzhen Dapeng Special Program for Industrial Development (No.
KY20150207), Special Project on the Integration of Industry, Education
and Research of Guangdong Province (No. 2013B090800017), Shenzhen
Scientific R&D Program (No. CXB201108250095A), State Key Laboratory of
Agricultural Genomics (No. ZDSY20120618171817275), and the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development at the National Institutes of Health,
USA.
NR 85
TC 0
Z9 0
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2047-217X
J9 GIGASCIENCE
JI GigaScience
PD APR 14
PY 2016
VL 5
AR 17
DI 10.1186/s13742-016-0122-9
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK0YG
UT WOS:000374638000001
PM 27087938
ER
PT J
AU Kilicoglu, H
Rosemblat, G
Fiszman, M
Rindflesch, TC
AF Kilicoglu, Halil
Rosemblat, Graciela
Fiszman, Marcelo
Rindflesch, Thomas C.
TI Sortal anaphora resolution to enhance relation extraction from
biomedical literature
SO BMC BIOINFORMATICS
LA English
DT Article
DE Natural language processing; Sortal anaphora resolution; Biomedical
literature; Semantic relation extraction
ID COREFERENCE RESOLUTION; DOMAIN; EVENT; CLASSIFICATION; AGREEMENT; TEXT
AB Background: Entity coreference is common in biomedical literature and it can affect text understanding systems that rely on accurate identification of named entities, such as relation extraction and automatic summarization. Coreference resolution is a foundational yet challenging natural language processing task which, if performed successfully, is likely to enhance such systems significantly. In this paper, we propose a semantically oriented, rule-based method to resolve sortal anaphora, a specific type of coreference that forms the majority of coreference instances in biomedical literature. The method addresses all entity types and relies on linguistic components of SemRep, a broad-coverage biomedical relation extraction system. It has been incorporated into SemRep, extending its core semantic interpretation capability from sentence level to discourse level.
Results: We evaluated our sortal anaphora resolution method in several ways. The first evaluation specifically focused on sortal anaphora relations. Our methodology achieved a F-1 score of 59.6 on the test portion of a manually annotated corpus of 320 Medline abstracts, a 4-fold improvement over the baseline method. Investigating the impact of sortal anaphora resolution on relation extraction, we found that the overall effect was positive, with 50 % of the changes involving uninformative relations being replaced by more specific and informative ones, while 35 % of the changes had no effect, and only 15 % were negative. We estimate that anaphora resolution results in changes in about 1.5 % of approximately 82 million semantic relations extracted from the entire PubMed.
Conclusions: Our results demonstrate that a heavily semantic approach to sortal anaphora resolution is largely effective for biomedical literature. Our evaluation and error analysis highlight some areas for further improvements, such as coordination processing and intra-sentential antecedent selection.
C1 [Kilicoglu, Halil; Rosemblat, Graciela; Fiszman, Marcelo; Rindflesch, Thomas C.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Kilicoglu, H (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM kilicogluh@mail.nih.gov
FU U.S. National Library of Medicine, National Institutes of Health
FX The authors thank Dongwook Shin for his assistance with the annotation
tool. This work was supported by the intramural research program at the
U.S. National Library of Medicine, National Institutes of Health.
NR 56
TC 1
Z9 1
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD APR 14
PY 2016
VL 17
AR 163
DI 10.1186/s12859-016-1009-6
PG 16
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DJ5WB
UT WOS:000374280400001
PM 27080229
ER
PT J
AU Temkin, SM
Minasian, L
Noone, AM
AF Temkin, Sarah M.
Minasian, Lori
Noone, Anne-Michelle
TI The End of the Hysterectomy Epidemic and Endometrial Cancer Incidence:
What Are the Unintended Consequences of Declining Hysterectomy Rates?
SO FRONTIERS IN ONCOLOGY
LA English
DT Review
DE hysterectomy; corpus uterus; endometrial; cancer
ID UNITED-STATES; RACIAL DISPARITIES; UTERINE-CANCER; BILATERAL
OOPHORECTOMY; CERVICAL-CANCER; PREVALENCE; TRENDS; WOMEN; IMPACT; CORPUS
AB Population-level cancer incidence rates are one measure to estimate the cancer burden. The goal is to provide information on trends to measure progress against cancer at the population level and identify emerging patterns signifying increased risk for additional research and intervention. Endometrial cancer is the most common of the gynecologic malignancies but capturing the incidence of disease among women at risk (i.e., women with a uterus) is challenging and not routinely published. Decreasing rates of hysterectomy increase the number of women at risk for disease, which should be reflected in the denominator of the incidence rate calculation. Furthermore, hysterectomy rates vary within the United States by multiple factors including geographic location, race, and ethnicity. Changing rates of hysterectomy are important to consider when looking at endometrial cancer trends. By correcting for hysterectomy when calculating incidence rates of cancers of the uterine corpus, many of the disparities that have been assumed for this disease are diminished.
C1 [Temkin, Sarah M.; Minasian, Lori] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Noone, Anne-Michelle] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Temkin, SM (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
EM sarah.temkin@nih.gov
NR 50
TC 0
Z9 0
U1 2
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD APR 14
PY 2016
VL 6
AR 89
DI 10.3389/fonc.2016.00089
PG 6
WC Oncology
SC Oncology
GA DJ4ZG
UT WOS:000374216000001
PM 27148481
ER
PT J
AU Zou, MF
Keck, TM
Kumar, V
Donthamsetti, P
Michino, M
Burzynski, C
Schweppe, C
Bonifazi, A
Free, RB
Sibley, DR
Janowsky, A
Shi, L
Javitch, JA
Newman, AH
AF Zou, Mu-Fa
Keck, Thomas M.
Kumar, Vivek
Donthamsetti, Prashant
Michino, Mayako
Burzynski, Caitlin
Schweppe, Catherine
Bonifazi, Alessandro
Free, R. Benjamin
Sibley, David R.
Janowsky, Aaron
Shi, Lei
Javitch, Jonathan A.
Newman, Amy Hauck
TI Novel Analogues of
(R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one
(Sumanirole) Provide Clues to Dopamine D-2/D-3 Receptor Agonist
Selectivity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID RESTLESS LEGS SYNDROME; D3 RECEPTOR; PARKINSONS-DISEASE; D-3 RECEPTORS;
FORCE-FIELD; D2 RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; MEDICINAL
CHEMISTRY; ANTAGONISTS; BINDING
AB Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D-2/D-3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [H-3]7-hydroxy-N,N-dipropy1-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [H-3]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both G(o)BRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy.
C1 [Zou, Mu-Fa; Keck, Thomas M.; Kumar, Vivek; Burzynski, Caitlin; Schweppe, Catherine; Bonifazi, Alessandro; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Michino, Mayako; Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Mol Targets & Medicat Discovery Branch,Intramural, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
[Donthamsetti, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA.
[Donthamsetti, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10027 USA.
[Donthamsetti, Prashant; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
[Free, R. Benjamin; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04, Bethesda, MD 20892 USA.
[Janowsky, Aaron] Vet Affairs Portland Hlth Care Syst, Res & Dev Serv, Portland, OR 97239 USA.
[Janowsky, Aaron] Oregon Hlth & Sci Univ, Sch Med, Dept Psychiat & Behav Neurosci, Portland, OR 97239 USA.
[Janowsky, Aaron] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA.
[Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
[Keck, Thomas M.] Rowan Univ, Coll Sci & Math, Dept Chem & Biochem, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
[Keck, Thomas M.] Rowan Univ, Coll Sci & Math, Dept Biomed & Translat Sci, 201 Mullica Hill Rd, Glassboro, NJ 08028 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Keck, Thomas/G-9798-2012; Kumar, Vivek/F-6183-2016
OI Keck, Thomas/0000-0003-1845-9373;
FU National Institute on Drug Abuse-Intramural Research Program; National
Institute of Neurological Disorders and Stroke Intramural Research
Program; National Institute on Drug Abuse/Department of Veterans Affairs
Interagency Agreement; Methamphetamine Abuse Research Center [P50
DA018165]; VA Merit Review and Senior Research Career Scientist
Programs; [K05 DA022413]; [R01 MH054137]
FX Support for this research was provided by the National Institute on Drug
Abuse-Intramural Research Program (A.H.N., M.-F.Z., V.K., T.M.K., A.B.,
C.B., C.S., L.S., and M.M.) and National Institute of Neurological
Disorders and Stroke Intramural Research Program (RB.F. and D.R.S.).
Support for J.A.J. and P.D. was provided by K05 DA022413 and R01
MH054137. Support for A.J. was provided by a National Institute on Drug
Abuse/Department of Veterans Affairs Interagency Agreement, by VA Merit
Review and Senior Research Career Scientist Programs, and by the
Methamphetamine Abuse Research Center (P50 DA018165). The authors thank
Dr. Robert Luedtke for earlier in vitro binding experiments on a subset
of these analogues. This work utilized the computational resources of
the NIH HPC Biowulf cluster (http://hpc.nih.gov).
NR 66
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PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD APR 14
PY 2016
VL 59
IS 7
BP 2973
EP 2988
DI 10.1021/acs.jmedchem.5b01612
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DJ7ZD
UT WOS:000374430800008
PM 27035329
ER
PT J
AU Lassalas, P
Gay, B
Lasfargeas, C
James, MJ
Tran, V
Vijayendran, KG
Brunden, KR
Kozlowski, MC
Thomas, CJ
Smith, AB
Huryn, DM
Ballatore, C
AF Lassalas, Pierrik
Gay, Bryant
Lasfargeas, Caroline
James, Michael J.
Van Tran
Vijayendran, Krishna G.
Brunden, Kurt R.
Kozlowski, Marisa C.
Thomas, Craig J.
Smith, Amos B., III
Huryn, Donna M.
Ballatore, Carlo
TI Structure Property Relationships of Carboxylic Acid Isosteres
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DRUG DESIGN; PROTEIN-BINDING; RECEPTOR ANTAGONISTS;
ASYMMETRIC-SYNTHESIS; MEDICINAL CHEMISTRY; HYDROXAMIC ACIDS; TETRAZOLE;
BIOISOSTERES; DERIVATIVES; INHIBITORS
AB The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the physicochemical properties of carboxylic acid isosteres would be desirable to enable more informed decisions of potential replacements to be used for analog design. Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres. The data set generated provides an assessment of the relative impact on the physicochemical properties that these replacements may have compared to the carboxylic acid analog. As such, this study presents a framework for how to rationally apply isosteric replacements of the carboxylic acid functional group.
C1 [Lassalas, Pierrik; Gay, Bryant; Lasfargeas, Caroline; Van Tran; Vijayendran, Krishna G.; Kozlowski, Marisa C.; Smith, Amos B., III; Huryn, Donna M.; Ballatore, Carlo] Univ Penn, Dept Chem, Sch Arts & Sci, 231 South 34th St, Philadelphia, PA 19104 USA.
[James, Michael J.; Brunden, Kurt R.; Ballatore, Carlo] Univ Penn, Ctr Neurodegenerat Dis Res, 3600 Spruce St, Philadelphia, PA 19104 USA.
[Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20850 USA.
RP Huryn, DM; Ballatore, C (reprint author), Univ Penn, Dept Chem, Sch Arts & Sci, 231 South 34th St, Philadelphia, PA 19104 USA.; Ballatore, C (reprint author), Univ Penn, Ctr Neurodegenerat Dis Res, 3600 Spruce St, Philadelphia, PA 19104 USA.
EM huryn@sas.upenn.edu; bcarlo@sas.upenn.edu
RI Lassalas, Pierrik/A-4944-2012;
OI Lassalas, Pierrik/0000-0001-9838-6973; Huryn, Donna/0000-0001-5542-4968
FU intramural program of National Center for Advancing Translational
Sciences; NIH/NIA [AG044332, AG034140]; NIH/NIGMS [GM87605]; Marian S.
Ware Alzheimer Program; NSF [CHE-0840438]
FX Financial support for this work has been provided in part by the
intramural program of the National Center for Advancing Translational
Sciences (CT), the NIH/NIA (AG044332; AG034140 for PL, BG, MJ, KB, and
CB), the NIH/NIGMS (GM87605 for MCK and VT), the Marian S. Ware
Alzheimer Program, and the NSF (Grant CHE-0840438, X-ray facility).
Finally, the authors would like to thank Mary Liang (University of
Pittsburgh) for careful reading of the manuscript.
NR 55
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PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD APR 14
PY 2016
VL 59
IS 7
BP 3183
EP 3203
DI 10.1021/acs.jmedchem.5b01963
PG 21
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DJ7ZD
UT WOS:000374430800023
PM 26967507
ER
PT J
AU Tosh, DK
Ciancetta, A
Warnick, E
O'Connor, R
Chen, ZM
Gizewski, E
Crane, S
Gao, ZG
Auchampach, JA
Salvemini, D
Jacobson, KA
AF Tosh, Dilip K.
Ciancetta, Antonella
Warnick, Eugene
O'Connor, Robert
Chen, Zhoumou
Gizewski, Elizabeth
Crane, Steven
Gao, Zhan-Guo
Auchampach, John A.
Salvemini, Daniela
Jacobson, Kenneth A.
TI Purine (N)-Methanocarba Nucleoside Derivatives Lacking an Exocyclic
Amine as Selective A(3) Adenosine Receptor Agonists
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CHRONIC NEUROPATHIC PAIN; A(2A) RECEPTOR; DRUG DESIGN; ANTAGONISTS;
BINDING; HYDROAMINATION; ACTIVATION; DISCOVERY; LIGANDS; ALKYNES
AB Purine (N)-methanocarba-5'-N-alkyluronamidoriboside A(3) adenosine receptor (A(3)AR) agonists lacking an exocyclic amine resulted from an unexpected reaction during a Sonogashira coupling and subsequent aminolysis. Because the initial C6-Me and C6-styryl derivatives had unexpectedly high A(3)AR affinity, other rigid nucleoside analogues lacking an exocyclic amine were prepared. Of these, the C6-Me-(2-phenylethynyl) and C2-(5-chlorothienylethynyl) analogues were particularly potent, with human A(3)AR K-i values of 6 and 42 nM, respectively. Additionally, the C2-(5-chlorothienyl)-6-H analogue was potent and selective at A(3)AR (MRS7220, K-i 60 nM) and also completely reversed mouse sciatic nerve mechanoallodynia (in vivo, 3 mu mol/kg, po). The lack of a C6 H-bond donor while maintaining A(3)AR affinity and efficacy could be rationalized by homology modeling and docking of these hypermodified nucleosides. The modeling suggests that a suitable combination of stabilizing features can partially compensate for the lack of an exocyclic amine, an otherwise important contributor to recognition in the A(3)AR binding site.
C1 [Tosh, Dilip K.; Ciancetta, Antonella; Warnick, Eugene; O'Connor, Robert; Crane, Steven; Gao, Zhan-Guo; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, NIH, Bldg 8A,Room B1A-19, Bethesda, MD 20892 USA.
[Chen, Zhoumou; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Gizewski, Elizabeth; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
RP Jacobson, KA (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, NIH, Bldg 8A,Room B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH Intramural Research Program (NIDDK) [ZIA DK031117-28]; National
Cancer Institute [R01CA169519]; National Heart Lung Institute
[R01HL077707, R01HL111392]; National Institute of Mental Health's
Psychoactive Drug Screening Program [HHSN-271-2008-00025-C]
FX We thank the NIH Intramural Research Program (NIDDK, ZIA DK031117-28);
National Cancer Institute (R01CA169519) and National Heart Lung
Institute (R01HL077707 and R01HL111392) for support and John Lloyd and
Noel Whittaker (NIDDK) for mass spectral determinations. We thank Dr.
Bryan L. Roth (University of North Carolina at Chapel Hill) and National
Institute of Mental Health's Psychoactive Drug Screening Program
(contract no. HHSN-271-2008-00025-C) for screening data.
NR 48
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PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD APR 14
PY 2016
VL 59
IS 7
BP 3249
EP 3263
DI 10.1021/acs.jmedchem.5b01998
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DJ7ZD
UT WOS:000374430800027
PM 26890707
ER
PT J
AU Ranade, AR
Higgins, L
Markowski, TW
Glaser, N
Kashin, D
Bai, RL
Hong, KH
Hamel, E
Hofle, G
Georg, GI
AF Ranade, Adwait R.
Higgins, LeeAnn
Markowski, Todd W.
Glaser, Nicole
Kashin, Dmitry
Bai, Ruoli
Hong, Kwon Ho
Hamel, Ernest
Hoefle, Gerhard
Georg, Gunda I.
TI Characterizing the Epothilone Binding Site on beta-Tubulin by
Photoaffinity Labeling: Identification of beta-Tubulin Peptides TARGSQQY
and TSRGSQQY as Targets of an Epothilone Photoprobe for Polymerized
Tubulin
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MICROTUBULE-STABILIZING AGENTS; CONFORMATION-ACTIVITY RELATIONSHIPS;
POLYKETIDE NATURAL-PRODUCTS; COMMON PHARMACOPHORE; SORANGIUM-CELLULOSUM;
BIOLOGICAL-ACTIVITY; CANCER-CELLS; MOUSE MODEL; SIDE-CHAIN; TAXOL
AB Photoaffinity labeling with an epothilone A photoprobe led to the identification of the beta-tubulin peptides TARGSQQY and TSRGSQQY as targets of the photoprobe for polymerized tubulin. These peptides represent residues 274-281 in different beta-tubulin isotypes. Placing the carbene producing 21-diazo/triazolo moiety of the photoprobe in the vicinity of the TARGSQQY peptide in a homology model of TBB3 predicted a binding pose and conformation of the photoprobe that are very similar to the ones reported for 1) the high resolution cocrystal structure of epothilone A with an alpha,beta-tubulin complex and for 2) a saturation transfer difference NMR and transferred NOESY NMR study of dimeric and polymerized tubulin. Our findings thus provide additional support for these models as physiologically the most relevant among several modes of binding that have been proposed for epothilone A in the taxane pocket of beta-tubulin.
C1 [Ranade, Adwait R.; Hong, Kwon Ho; Georg, Gunda I.] Univ Minnesota, Coll Pharm, Dept Med Chem, 717 Delaware St SE, Minneapolis, MN 55414 USA.
[Ranade, Adwait R.; Hong, Kwon Ho; Georg, Gunda I.] Univ Minnesota, Coll Pharm, Inst Therapeut Discovery & Dev, 717 Delaware St SE, Minneapolis, MN 55414 USA.
[Higgins, LeeAnn; Markowski, Todd W.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, 321 Church St SE, Minneapolis, MN 55455 USA.
[Glaser, Nicole; Kashin, Dmitry; Hoefle, Gerhard] Helmholtz Ctr Infect Res, Dept Nat Prod Chem, Inhoffenstr 7, D-38124 Braunschweig, Germany.
[Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
RP Georg, GI (reprint author), Univ Minnesota, Coll Pharm, Dept Med Chem, 717 Delaware St SE, Minneapolis, MN 55414 USA.; Georg, GI (reprint author), Univ Minnesota, Coll Pharm, Inst Therapeut Discovery & Dev, 717 Delaware St SE, Minneapolis, MN 55414 USA.
EM georg@umn.edu
FU University of Minnesota through Vince and McKnight Endowed Chairs; NSF
Major Research Instrumentation Grant [9871237]; NSF [CHE-0078192]; NIH
Multiuser Grant [RR15808, 2001-2002]; NSF-MRI Grant [0215759]; State of
Minnesota Infrastructure Grant; University of Minnesota - College of
Agriculture, Food and Environmental Sciences; College of Biological
Sciences; Minnesota Graduate School; Minnesota Medical Foundation;
Department of Biochemistry, Molecular Biology and Biophysics; Office of
the Vice President for Health Sciences; Vice President for Research
FX We greatly appreciate the financial support from the University of
Minnesota through the Vince and McKnight Endowed Chairs (to G.I.G.). We
thank Florenz Sasse for performing cell cytotoxicity and tubulin
assembly assays. The authors recognize the Center for Mass Spectrometry
and Proteomics at the University of Minnesota and various supporting
agencies, including NSF Major Research Instrumentation Grant 9871237,
NSF Grant CHE-0078192, NIH Multiuser Grant RR15808, 2001-2002, NSF-MRI
Grant 0215759, State of Minnesota Infrastructure Grant, and University
of Minnesota support from the College of Agriculture, Food and
Environmental Sciences, the College of Biological Sciences, the
Minnesota Graduate School, the Minnesota Medical Foundation, the
Department of Biochemistry, Molecular Biology and Biophysics, the Office
of the Vice President for Health Sciences, and the Vice President for
Research. See http://www.cbs.umn.edu/research/resources/msp/about. We
also thank the Minnesota Supercomputing Institute for their support for
the computational study.
NR 61
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PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD APR 14
PY 2016
VL 59
IS 7
BP 3499
EP 3514
DI 10.1021/acs.jmedchem.6b00188
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DJ7ZD
UT WOS:000374430800044
PM 26986898
ER
PT J
AU Castro, NP
Merchant, AS
Saylor, KL
Anver, MR
Salomon, DS
Golubeva, YG
AF Castro, Nadia P.
Merchant, Anand S.
Saylor, Karen L.
Anver, Miriam R.
Salomon, David S.
Golubeva, Yelena G.
TI Adaptation of Laser Microdissection Technique for the Study of a
Spontaneous Metastatic Mammary Carcinoma Mouse Model by NanoString
Technologies
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION ANALYSIS; MICROCAPILLARY ELECTROPHORESIS TRACES; CAPTURE
MICRODISSECTION; BREAST-CANCER; RNA QUALITY; TISSUE SAMPLES; IMPACT;
TARGET
AB Laser capture microdissection (LCM) of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform. In this present manuscript we describe in detail the adaptation of LCM methodology for the collection and preparation of fresh frozen samples for NanoString analysis based on a study of a model of mouse mammary gland carcinoma and its lung metastasis. Our adaptation of LCM sample preparation and workflow to the requirements of the NanoString platform allowed acquiring samples with high RNA quality. The NanoString analysis of such samples provided sensitive detection of genes of interest and their associated molecular pathways. NanoString is a reliable gene expression analysis platform that can be effectively coupled with LCM.
C1 [Castro, Nadia P.; Saylor, Karen L.; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Merchant, Anand S.] NCI, CCRIFX Bioinformat Core, Bethesda, MD 20892 USA.
[Anver, Miriam R.; Golubeva, Yelena G.] Leidos Biomed Res Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Castro, NP (reprint author), NCI, Tumor Growth Factor Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA.; Golubeva, YG (reprint author), Leidos Biomed Res Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM castron2@mail.nih.gov; yelena.golubeva@gmail.com
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 24
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U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 14
PY 2016
VL 11
IS 4
AR e0153270
DI 10.1371/journal.pone.0153270
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ3UH
UT WOS:000374131700034
PM 27077656
ER
PT J
AU Zurawski, G
Zurawski, S
Flamar, AL
Richert, L
Wagner, R
Tomaras, GD
Montefiori, DC
Roederer, M
Ferrari, G
Lacabaratz, C
Bonnabau, H
Klucar, P
Wang, ZQ
Foulds, KE
Kao, SF
Yates, NL
LaBranche, C
Jacobs, BL
Kibler, K
Asbach, B
Kliche, A
Salazar, A
Reed, S
Self, S
Gottardo, R
Galmin, L
Weiss, D
Cristillo, A
Thiebaut, R
Pantaleo, G
Levy, Y
AF Zurawski, Gerard
Zurawski, Sandra
Flamar, Anne-Laure
Richert, Laura
Wagner, Ralf
Tomaras, Georgia D.
Montefiori, David C.
Roederer, Mario
Ferrari, Guido
Lacabaratz, Christine
Bonnabau, Henri
Klucar, Peter
Wang, Zhiqing
Foulds, Kathryn E.
Kao, Shing-Fen
Yates, Nicole L.
LaBranche, Celia
Jacobs, Bertram L.
Kibler, Karen
Asbach, Benedikt
Kliche, Alexander
Salazar, Andres
Reed, Steve
Self, Steve
Gottardo, Raphael
Galmin, Lindsey
Weiss, Deborah
Cristillo, Anthony
Thiebaut, Rodolphe
Pantaleo, Giuseppe
Levy, Yves
TI Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus
Macaques
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; NONHUMAN-PRIMATES; DENDRITIC CELLS; EFFICACY TRIAL;
IMMUNOLOGICAL CHARACTERIZATION; LANGERHANS CELLS; VACCINIA VIRUS;
ANTIBODIES; PROTEIN; ANTIGENS
AB Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4(+) and CD8(+) Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4(+) T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1.
C1 [Zurawski, Gerard; Zurawski, Sandra; Flamar, Anne-Laure; Lacabaratz, Christine; Klucar, Peter; Wang, Zhiqing; Levy, Yves] Univ Paris Est, Vaccine Res Inst, Fac Med, INSERM,U955, Creteil, France.
[Zurawski, Gerard; Zurawski, Sandra; Flamar, Anne-Laure; Lacabaratz, Christine; Klucar, Peter; Wang, Zhiqing; Levy, Yves] Grp Henri Mondor Albert Chenevier, AP HP, Serv Immunol Clin, INRIA SISTM, Creteil, France.
[Zurawski, Gerard; Zurawski, Sandra; Flamar, Anne-Laure; Klucar, Peter; Wang, Zhiqing] Baylor Inst Immunol Res, Dallas, TX USA.
[Zurawski, Gerard; Zurawski, Sandra; Flamar, Anne-Laure; Klucar, Peter; Wang, Zhiqing] INSERM, U955, Dallas, TX USA.
[Richert, Laura; Bonnabau, Henri; Thiebaut, Rodolphe] Univ Bordeaux Segalen, INSERM, U897, INRIA SISTM, Bordeaux, France.
[Wagner, Ralf; Asbach, Benedikt; Kliche, Alexander] Univ Regensburg, Inst Med Microbiol & Hyg, Mol Microbiol & Gene Therapy Unit, D-93053 Regensburg, Germany.
[Tomaras, Georgia D.; Montefiori, David C.; Ferrari, Guido; Yates, Nicole L.; LaBranche, Celia] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Tomaras, Georgia D.; Montefiori, David C.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Roederer, Mario; Foulds, Kathryn E.; Kao, Shing-Fen] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Jacobs, Bertram L.; Kibler, Karen] Arizona State Univ, Sch Life Sci, Ctr Infect Dis & Vaccinol, Tempe, AZ USA.
[Self, Steve; Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Self, Steve; Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Salazar, Andres] Oncovir, Washington, DC USA.
[Reed, Steve] Infect Dis Res Inst, Seattle, WA USA.
[Galmin, Lindsey; Weiss, Deborah; Cristillo, Anthony] Adv BioSci Labs Inc, Rockville, MD USA.
[Pantaleo, Giuseppe] CHU Vaudois, CH-101 Lausanne, Switzerland.
RP Zurawski, G (reprint author), Univ Paris Est, Vaccine Res Inst, Fac Med, INSERM,U955, Creteil, France.; Zurawski, G (reprint author), Grp Henri Mondor Albert Chenevier, AP HP, Serv Immunol Clin, INRIA SISTM, Creteil, France.; Zurawski, G (reprint author), Baylor Inst Immunol Res, Dallas, TX USA.
EM gerardz@baylorhealth.edu
RI Tomaras, Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016;
OI Zurawski, Gerard/0000-0002-0168-3523
FU Vaccine Research Institute HIV vaccine program (ANRS/INSERM); Vaccine
Research Institute HIV vaccine program (Investissements d'Avenir
program) [ANR-10-LABX-77]; Poxvirus T-cell Vaccine Consortium - Bill &
Melinda Gates Foundation [OPP38599]; Vaccine Immune Monitoring Centers -
Bill & Melinda Gates Foundation [OPP1032325, OPP1032144]; Vaccine
Immunology Statistical Center - Bill & Melinda Gates Foundation
[OPP1032317]
FX The study was funded within the Vaccine Research Institute HIV vaccine
program (ANRS/INSERM and was supported by the Investissements d'Avenir
program managed by the ANR under reference ANR-10-LABX-77). Support from
the Poxvirus T-cell Vaccine Consortium funded by the Bill & Melinda
Gates Foundation (OPP38599) for the development of NYVAC-KC vector.
Support for the ICS and antibody immune monitoring assays was provided
by the Vaccine Immune Monitoring Centers (OPP1032325 & OPP1032144), and
support for the statistical analysis from the Vaccine Immunology
Statistical Center (OPP1032317), all part of the Collaboration for AIDS
Vaccine Discovery (CAVD) funded by the Bill & Melinda Gates Foundation.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; The study was
funded within the Vaccine Research Institute HIV vaccine program
(ANRS/INSERM and was supported by the Investissements d'Avenir program
managed by the ANR under reference ANR-10-LABX-77). Support from the
Poxvirus T-cell Vaccine Consortium funded by the Bill & Melinda Gates
Foundation (OPP38599) for the development of NYVAC-KC vector. Support
for the ICS and antibody immune monitoring assays was provided by the
Vaccine Immune Monitoring Centers (OPP1032325 & OPP1032144), and support
for the statistical analysis from the Vaccine Immunology Statistical
Center (OPP1032317), all part of the Collaboration for AIDS Vaccine
Discovery (CAVD) funded by the Bill & Melinda Gates Foundation. Alicia
Sato (Statistical Center for HIV/AIDS Research and Prevention, Fred
Hutchinson Cancer Research Center) and Jason Skinner (BIIR) are thanked
for valuable edits. Matthew Baker (Antitope, Ltd) provided humanization
of the alpha LOX-1 15C4 mAb. Lauren Hudacik (ABL), Cecile Peltekian
(INSERM U955) and Song Ding (EuroVacc Foundation) are thanked for
excellent project coordination.
NR 43
TC 1
Z9 1
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 14
PY 2016
VL 11
IS 4
AR e0153484
DI 10.1371/journal.pone.0153484
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ3UH
UT WOS:000374131700063
PM 27077384
ER
PT J
AU Kaur, A
Webster, MR
Marchbank, K
Behera, R
Ndoye, A
Kugel, CH
Dang, VM
Appleton, J
O'Connell, MP
Cheng, P
Valiga, AA
Morissette, R
McDonnell, NB
Ferrucci, L
Kossenkov, AV
Meeth, K
Tang, HY
Yin, XF
Wood, WH
Lehrmann, E
Becker, KG
Flaherty, KT
Frederick, DT
Wargo, JA
Cooper, ZA
Tetzlaff, MT
Hudgens, C
Aird, KM
Zhang, RG
Xu, XW
Liu, Q
Bartlett, E
Karakousis, G
Eroglu, Z
Lo, RS
Chan, M
Menzies, AM
Long, GV
Johnson, DB
Sosman, J
Schilling, B
Schadendorf, D
Speicher, DW
Bosenberg, M
Ribas, A
Weeraratna, AT
AF Kaur, Amanpreet
Webster, Marie R.
Marchbank, Katie
Behera, Reeti
Ndoye, Abibatou
Kugel, Curtis H., III
Dang, Vanessa M.
Appleton, Jessica
O'Connell, Michael P.
Cheng, Phil
Valiga, Alexander A.
Morissette, Rachel
McDonnell, Nazli B.
Ferrucci, Luigi
Kossenkov, Andrew V.
Meeth, Katrina
Tang, Hsin-Yao
Yin, Xiangfan
Wood, William H., III
Lehrmann, Elin
Becker, Kevin G.
Flaherty, Keith T.
Frederick, Dennie T.
Wargo, Jennifer A.
Cooper, Zachary A.
Tetzlaff, Michael T.
Hudgens, Courtney
Aird, Katherine M.
Zhang, Rugang
Xu, Xiaowei
Liu, Qin
Bartlett, Edmund
Karakousis, Giorgos
Eroglu, Zeynep
Lo, Roger S.
Chan, Matthew
Menzies, Alexander M.
Long, Georgina V.
Johnson, Douglas B.
Sosman, Jeffrey
Schilling, Bastian
Schadendorf, Dirk
Speicher, David W.
Bosenberg, Marcus
Ribas, Antoni
Weeraratna, Ashani T.
TI sFRP2 in the aged microenvironment drives melanoma metastasis and
therapy resistance
SO NATURE
LA English
DT Article
ID BETA-CATENIN; OXIDATIVE STRESS; CELLS; TUMOR; GROWTH; PROGRESSION;
PHENOTYPE; CANCER; MITF
AB Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression(1-4), we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. Here we find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade in melanoma cells that results in a decrease in beta-catenin and microphthalmia-associated transcription factor (MITF), and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA damage induced by reactive oxygen species, rendering the cells more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumour progression, offering new possibilities for the design of therapy for the elderly.
C1 [Kaur, Amanpreet; Webster, Marie R.; Marchbank, Katie; Behera, Reeti; Ndoye, Abibatou; Kugel, Curtis H., III; Dang, Vanessa M.; Appleton, Jessica; O'Connell, Michael P.; Valiga, Alexander A.; Kossenkov, Andrew V.; Tang, Hsin-Yao; Yin, Xiangfan; Aird, Katherine M.; Zhang, Rugang; Liu, Qin; Speicher, David W.; Weeraratna, Ashani T.] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Kaur, Amanpreet] Univ Sci, Philadelphia, PA 19104 USA.
[Cheng, Phil] Univ Zurich, Dept Dermatol, CH-8006 Zurich, Switzerland.
[Morissette, Rachel; McDonnell, Nazli B.; Ferrucci, Luigi; Wood, William H., III; Lehrmann, Elin; Becker, Kevin G.] NIA, NIH, Baltimore, MD 21224 USA.
[Meeth, Katrina; Bosenberg, Marcus] Yale Univ, Dept Dermatol & Pathol, New Haven, CT 06511 USA.
[Flaherty, Keith T.; Frederick, Dennie T.] Massachusetts Gen Hosp, Ctr Canc, Dev Therapeut, Boston, MA 02114 USA.
[Wargo, Jennifer A.; Cooper, Zachary A.; Tetzlaff, Michael T.; Hudgens, Courtney] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Xu, Xiaowei; Bartlett, Edmund; Karakousis, Giorgos] Univ Penn, Dept Surg, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Xu, Xiaowei; Bartlett, Edmund; Karakousis, Giorgos] Univ Penn, Dept Pathol, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Eroglu, Zeynep] City Hope Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA.
[Lo, Roger S.; Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Chan, Matthew] Westmead Hosp, Crown Princess Mary Canc Ctr, Westmead, NSW 2145, Australia.
[Menzies, Alexander M.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW 2000, Australia.
[Menzies, Alexander M.; Long, Georgina V.] Univ Sydney, Sydney, NSW 2000, Australia.
[Johnson, Douglas B.; Sosman, Jeffrey] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA.
[Schilling, Bastian; Schadendorf, Dirk] Univ Duesburg Essen, Dept Dermatol, Univ Hosp, West German Canc Ctr, Essen, Germany.
[Schilling, Bastian; Schadendorf, Dirk] German Canc Consortium DKTK, D-45127 Heidelberg, Germany.
RP Weeraratna, AT (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM aweeraratna@wistar.org
OI Bartlett, Edmund/0000-0002-0923-153X; Cooper,
Zachary/0000-0003-1059-0940
FU National Institute on Aging, Baltimore, Maryland; Harry J. Lloyd
Foundation; ACS-IRG; Melanoma Research Foundation; Cancer Center Support
Grant [P30 CA010815]; [P01 CA 114046-06]; [T32 CA 9171-36]; [RO1
CA174746-01]
FX We thank D. Altieri, R. Marais, Z. Ronai, M. McMahon, and B. Vogelstein
for comments on the manuscript. We thank R. Somasundaram for advice on
immune analyses, M. Herlyn for the WM cell lines, and G. Bollag for
PLX4720. We also thank R. Delgiacco, D. Gourevitch, F. Keeney, and D.
Schultz. We thank A. Dias-Wanigasekera, E. Gaddy, and M. Ha for
technical assistance, and R. Locke for editing the manuscript. This work
was supported in part by funds from the Intramural Program of the
National Institute on Aging, Baltimore, Maryland (N.M., K.G.B., R. M.,
W.H.W., L.F.), The Harry J. Lloyd Foundation (K.M., A.T.W.), P01 CA
114046-06 (A.T.W., Q.L.), T32 CA 9171-36 (M.R.W., C.H.K.), an ACS-IRG
award (A.T.W.), the Melanoma Research Foundation (A.T.W.), and RO1
CA174746-01 (A.T.W., A.K.). Core facilities at the Wistar are supported
by Cancer Center Support Grant P30 CA010815.
NR 29
TC 20
Z9 20
U1 9
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 250
EP +
DI 10.1038/nature17392
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100043
PM 27042933
ER
PT J
AU Zou, M
Baitei, EY
Al-Rijjal, RA
Parhar, RS
Al-Mohanna, FA
Kimura, S
Pritchard, C
Binessa, HA
Alzahrani, AS
Al-Khalaf, HH
Hawwari, A
Akhtar, M
Assiri, AM
Meyer, BF
Shi, Y
AF Zou, M.
Baitei, E. Y.
Al-Rijjal, R. A.
Parhar, R. S.
Al-Mohanna, F. A.
Kimura, S.
Pritchard, C.
Binessa, H. A.
Alzahrani, A. S.
Al-Khalaf, H. H.
Hawwari, A.
Akhtar, M.
Assiri, A. M.
Meyer, B. F.
Shi, Y.
TI TSH overcomes Braf(V600E)-induced senescence to promote tumor
progression via downregulation of p53 expression in papillary thyroid
cancer
SO ONCOGENE
LA English
DT Article
ID ONCOGENE-INDUCED SENESCENCE; SERUM TSH; TRANSGENIC MICE; BRAF MUTATIONS;
MOUSE MODEL; IN-VIVO; CARCINOMA; PTEN; CELLS; RAS
AB The BRAF(V600E) mutation is found in approximately 40% of papillary thyroid cancers (PTC). Mice with thyroid-specific expression of BRAF(V600E) (TPO-BRAF(V600E)) develop PTC rapidly with high levels of serum thyroid-stimulating hormone (TSH). It is unclear to what extent the elevated TSH contributes to tumor progression. To investigate the progression of BRAF(V600E)-induced PTC (BVE-PTC) under normal TSH, we transplanted BVE-PTC tumors subcutaneously into nude and TPO-Braf(WT) mice. Regression of the transplanted tumors was observed in both nude and TPO-Braf(WT) mice. They were surrounded by heavy lymphocyte infiltration and oncogene-induced senescence (OIS) was demonstrated by strong beta-gal staining and absence of Ki-67 expression. In contrast, BVE-PTC transplants continued to grow when transplanted into TPO-BRAF(V600E) mice. The expression of Trp53 was increased in tumor transplants undergoing OIS. Trp53 inactivation reversed OIS and enabled tumor transplants to grow in nude mice with characteristic cell morphology of anaplastic thyroid cancer (ATC). PTC-to-ATC transformation was also observed in primary BVE-PTC tumors. ATC cells derived from Trp53 knockout tumors had increased PI3K/AKT signaling and became resistant to BRAF(V600E) inhibitor PLX4720, which could be overcome by combined treatment of PI3K inhibitor LY294002 and PLX4720. In conclusion, BVE-PTC progression could be contained via p53-dependent OIS and TSH is a major disruptor of this balance. Simultaneous targeting of both MAPK and PI3K/AKT pathways offer a better therapeutic outcome against ATC. The current study reinforces the importance of rigorous control of serum TSH in PTC patients.
C1 [Zou, M.; Baitei, E. Y.; Al-Rijjal, R. A.; Binessa, H. A.; Hawwari, A.; Meyer, B. F.; Shi, Y.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, MBC 3,Takhassusi St,POB 3354, Riyadh 11211, Saudi Arabia.
[Parhar, R. S.; Al-Mohanna, F. A.] King Faisal Specialist Hosp & Res Ctr, Dept Cell Biol, Riyadh 11211, Saudi Arabia.
[Kimura, S.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Pritchard, C.] Univ Leicester, Dept Biochem, Lancaster Rd, Leicester LE1 7RH, Leics, England.
[Alzahrani, A. S.] King Faisal Specialist Hosp & Res Ctr, Dept Med, POB 3354, Riyadh 11211, Saudi Arabia.
[Al-Khalaf, H. H.] King Faisal Specialist Hosp & Res Ctr, Dept Mol Oncol, Riyadh 11211, Saudi Arabia.
[Akhtar, M.] King Faisal Specialist Hosp & Res Ctr, Dept Pathol, POB 3354, Riyadh 11211, Saudi Arabia.
[Assiri, A. M.] King Faisal Specialist Hosp & Res Ctr, Dept Comparat Med, Riyadh 11211, Saudi Arabia.
RP Shi, Y (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Genet, MBC 3,Takhassusi St,POB 3354, Riyadh 11211, Saudi Arabia.
EM yufei@kfshrc.edu.sa
FU KACST [11-BIO1434-20]
FX We would like to thank Mr Wilfredo Antiquera for excellent technical
support. This study is supported by KACST grant 11-BIO1434-20.
NR 59
TC 0
Z9 0
U1 8
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD APR 14
PY 2016
VL 35
IS 15
BP 1909
EP 1918
DI 10.1038/onc.2015.253
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DJ2CC
UT WOS:000374010300004
PM 26477313
ER
PT J
AU Du Toit, G
Sayre, PH
Roberts, G
Sever, ML
Lawson, K
Bahnson, HT
Brough, HA
Santos, AF
Harris, KM
Radulovic, S
Basting, M
Turcanu, V
Plaut, M
Lack, G
AF Du Toit, George
Sayre, Peter H.
Roberts, Graham
Sever, Michelle L.
Lawson, Kaitie
Bahnson, Henry T.
Brough, Helen A.
Santos, Alexandra F.
Harris, Kristina M.
Radulovic, Suzana
Basting, Monica
Turcanu, Victor
Plaut, Marshall
Lack, Gideon
CA Immune Tolerance Network LEAP-On
TI Effect of Avoidance on Peanut Allergy after Early Peanut Consumption
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TERM CLINICAL-EFFICACY; FOOD ALLERGY; ORAL IMMUNOTHERAPY; ANAPHYLAXIS;
EPIDEMIOLOGY; MANAGEMENT; CHILDREN; INFANTS; PROTEIN; EUROPE
AB BACKGROUND
In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group).
METHODS
At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age.
RESULTS
We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P< 0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P = 0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4: IgE ratio.
CONCLUSIONS
Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known.
C1 [Du Toit, George; Brough, Helen A.; Santos, Alexandra F.; Radulovic, Suzana; Basting, Monica; Turcanu, Victor; Lack, Gideon] Kings Coll London, Div Asthma Allergy & Lung Biol, Dept Pediat Allergy, London, England.
[Du Toit, George; Brough, Helen A.; Santos, Alexandra F.; Radulovic, Suzana; Basting, Monica; Turcanu, Victor; Lack, Gideon] Guys & St Thomas NHS Fdn Trust, London, England.
[Roberts, Graham] Univ Southampton, Southampton, Hants, England.
[Roberts, Graham] Natl Inst Hlth Res Resp, Biomed Res Unit, Southampton, Hants, England.
[Roberts, Graham] David Hide Ctr, Newport, Isle Of Wight, England.
[Sayre, Peter H.] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA 94143 USA.
[Sever, Michelle L.; Lawson, Kaitie; Bahnson, Henry T.] Rho Fed Syst Div, Chapel Hill, NC USA.
[Harris, Kristina M.] Immune Tolerance Network, Bethesda, MD USA.
[Plaut, Marshall] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Lack, G (reprint author), Guys & St Thomas NHS Fdn Trust, Childrens Allergy Unit, 2nd Fl,South Wing,Westminster Bridge Rd, London SE1 7EH, England.
EM gideon.lack@kcl.ac.uk
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [NO1-AI-15416, UM1AI109565, HHSN272200800029C,
UM2AI117870]; Food Allergy Research and Education; Medical Research
Council; Asthma U.K. Centre; U.K. Department of Health through a
National Institute for Health Research comprehensive Biomedical Research
Centre; King's College London; King's College Hospital NHS Foundation
Trust; National Peanut Board, Atlanta; U.K. Food Standards Agency
FX Supported by grants (NO1-AI-15416, UM1AI109565, HHSN272200800029C, and
UM2AI117870) from the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health and by Food Allergy
Research and Education, the Medical Research Council and Asthma U.K.
Centre, and the U.K. Department of Health through a National Institute
for Health Research comprehensive Biomedical Research Centre award to
Guy's and St. Thomas' NHS Foundation Trust, in partnership with King's
College London and King's College Hospital NHS Foundation Trust. The
clinical trials unit was supported by the National Peanut Board,
Atlanta. The U.K. Food Standards Agency provided additional support for
the costs of phlebotomy.
NR 16
TC 48
Z9 48
U1 10
U2 17
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 14
PY 2016
VL 374
IS 15
BP 1435
EP 1443
DI 10.1056/NEJMoa1514209
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ3TD
UT WOS:000374128400007
PM 26942922
ER
PT J
AU Berthon, A
Drelon, C
Val, P
AF Berthon, Annabel
Drelon, Coralie
Val, Pierre
TI Pregnancy, Primary Aldosteronism, and Somatic CTNNB1 Mutations
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID ADENOMA
C1 [Berthon, Annabel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Drelon, Coralie; Val, Pierre] Ctr Natl Rech Sci, UMR 6293, Clermont Ferrand, France.
RP Val, P (reprint author), Ctr Natl Rech Sci, UMR 6293, Clermont Ferrand, France.
EM pierre.val@univ-bpclermont.fr
NR 4
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 14
PY 2016
VL 374
IS 15
BP 1493
EP 1494
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ3TD
UT WOS:000374128400023
PM 27074082
ER
PT J
AU Ribas, V
Drew, BG
Zhou, ZQ
Phun, J
Kalajian, NY
Soleymani, T
Daraei, P
Widjaja, K
Wanagat, J
Vallim, TQD
Fluitt, AH
Bensinger, S
Le, T
Radu, C
Whitelegge, JP
Beaven, SW
Tontonoz, P
Lusis, AJ
Parks, BW
Vergnes, L
Reue, K
Singh, H
Bopassa, JC
Toro, L
Stefani, E
Watt, MJ
Schenk, S
Akerstrom, T
Kelly, M
Pedersen, BK
Hewitt, SC
Korach, KS
Hevener, AL
AF Ribas, Vicent
Drew, Brian G.
Zhou, Zhenqi
Phun, Jennifer
Kalajian, Nareg Y.
Soleymani, Teo
Daraei, Pedram
Widjaja, Kevin
Wanagat, Jonathan
Vallim, Thomas Q. de Aguiar
Fluitt, Amy H.
Bensinger, Steven
Thuc Le
Radu, Caius
Whitelegge, Julian P.
Beaven, Simon W.
Tontonoz, Peter
Lusis, Aldons J.
Parks, Brian W.
Vergnes, Laurent
Reue, Karen
Singh, Harpreet
Bopassa, Jean C.
Toro, Ligia
Stefani, Enrico
Watt, Matthew J.
Schenk, Simon
Akerstrom, Thorbjorn
Kelly, Meghan
Pedersen, Bente K.
Hewitt, Sylvia C.
Korach, Kenneth S.
Hevener, Andrea L.
TI Skeletal muscle action of estrogen receptor a is critical for the
maintenance of mitochondrial function and metabolic homeostasis in
females
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PERMEABILITY TRANSITION PORE; INDUCED INSULIN-RESISTANCE; SYNDROME
CRITICAL REGION; FISSION PROTEIN DRP1; ER-ALPHA; AUTOPHAGOSOMAL
DEGRADATION; MONITORING AUTOPHAGY; OXIDATIVE-METABOLISM; INHIBITS
CALCINEURIN; ADIPOSE-TISSUE
AB Impaired estrogen receptor a (ERa) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERa expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERa knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overproduction of reactive oxygen species, and impairment in basal and stress-induced mitochondrial fission dynamics, driven by imbalanced protein kinase A-regulator of calcineurin 1-calcineurin signaling through dynamin-related protein 1, tracked with reduced oxidative metabolism in MERKO muscle. Although muscle mitochondrial DNA (mtDNA) abundance was similar between the genotypes, ERa deficiency diminished mtDNA turnover by a balanced reduction in mtDNA replication and degradation. Our findings indicate the retention of dysfunctional mitochondria in MERKO muscle and implicate ERa in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women.
C1 [Ribas, Vicent; Drew, Brian G.; Zhou, Zhenqi; Phun, Jennifer; Kalajian, Nareg Y.; Soleymani, Teo; Daraei, Pedram; Widjaja, Kevin; Fluitt, Amy H.; Hevener, Andrea L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA.
[Wanagat, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA.
[Vallim, Thomas Q. de Aguiar; Lusis, Aldons J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA.
[Fluitt, Amy H.; Bensinger, Steven; Thuc Le; Radu, Caius] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Thuc Le; Radu, Caius] Univ Calif Los Angeles, David Geffen Sch Med, Ahmanson Translat Imaging Div, Los Angeles, CA 90095 USA.
[Whitelegge, Julian P.] Univ Calif Los Angeles, David Geffen Sch Med, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA.
[Whitelegge, Julian P.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Neuropsychiat Inst, Los Angeles, CA 90095 USA.
[Beaven, Simon W.; Tontonoz, Peter] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
[Beaven, Simon W.; Tontonoz, Peter] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Lusis, Aldons J.; Parks, Brian W.; Vergnes, Laurent; Reue, Karen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Singh, Harpreet; Bopassa, Jean C.; Toro, Ligia; Stefani, Enrico] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA.
[Watt, Matthew J.] Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia.
[Schenk, Simon] Univ Calif San Diego, Dept Orthopaed Surg, La Jolla, CA 92093 USA.
[Akerstrom, Thorbjorn; Kelly, Meghan; Pedersen, Bente K.] Univ Copenhagen, Rigshosp, Ctr Inflammat & Metab, DK-2200 Copenhagen, Denmark.
[Akerstrom, Thorbjorn; Kelly, Meghan; Pedersen, Bente K.] Univ Copenhagen, Rigshosp, Ctr Phys Act Res, DK-2200 Copenhagen, Denmark.
[Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Hevener, Andrea L.] UCLA Iris Cantor Womens Hlth Res Ctr, Los Angeles, CA 90095 USA.
[Kelly, Meghan] Univ Rochester, Sch Med & Dent, Dept Orthopaed & Rehabil, Rochester, NY 14642 USA.
RP Hevener, AL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA.; Hevener, AL (reprint author), UCLA Iris Cantor Womens Hlth Res Ctr, Los Angeles, CA 90095 USA.
EM ahevener@mednet.ucla.edu
RI Watt, Matthew/B-2089-2014;
OI Korach, Kenneth/0000-0002-7765-418X; Pedersen, Bente
Klarlund/0000-0001-6508-6288; Singh, Harpreet/0000-0002-6135-1897
FU NIH [DK060484, DK073227, HL28481, HL30568, DK063491]; Nuclear Receptor
Signaling Atlas (NURSA) Data Source Project [DK097748]; UCLA Department
of Medicine; UCLA Iris Cantor Women's Health Center-UCLA Clinical and
Translational Science Institute [UL1TR000124]; Spanish Ministry of
Health; Australian National Health and Medical Research Council; UCLA
Jonsson Comprehensive Cancer Center; Danish National Research Foundation
[DNRF55]; NIH R00 [HL123021]; NIH National Center for Research Resources
[S10RR026744]
FX These studies were supported in part by research grants from the NIH
[DK060484, DK073227, and Nuclear Receptor Signaling Atlas (NURSA) Data
Source Project grant DK097748], UCLA Department of Medicine, and UCLA
Iris Cantor Women's Health Center-UCLA Clinical and Translational
Science Institute (UL1TR000124) to A.L.H. and Z.Z. V.R. was supported by
the Spanish Ministry of Health, and B.G.D. was supported by the
Australian National Health and Medical Research Council and the UCLA
Jonsson Comprehensive Cancer Center. During the study period, the Centre
of Inflammation and Metabolism was supported by a grant from the Danish
National Research Foundation (DNRF55) to B.K.P. A.J.L. is supported by
NIH (grants HL28481 and HL30568), and B.W.P. is supported by NIH R00
grant HL123021. The Centre for Physical Activity Research is supported
by a grant from TrygFonden. A.J.L. is supported by NIH grants HL28481
and HL30568, and L.V. and K.R. are supported in part by NIH grant
HL28481. The Seahorse XF24 instrument was acquired by a shared
instrument grant from the NIH National Center for Research Resources
(S10RR026744). P.T. is an investigator of the Howard Hughes Medical
Institute and is supported by NIH (DK063491).
NR 86
TC 6
Z9 6
U1 2
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 13
PY 2016
VL 8
IS 334
AR 334ra54
DI 10.1126/scitranslmed.aad3815
PG 21
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DJ5IW
UT WOS:000374241500006
PM 27075628
ER
PT J
AU Brazhnik, E
McCoy, AJ
Novikov, N
Hatch, CE
Walters, JR
AF Brazhnik, Elena
McCoy, Alex J.
Novikov, Nikolay
Hatch, Christina E.
Walters, Judith R.
TI Ventral Medial Thalamic Nucleus Promotes Synchronization of Increased
High Beta Oscillatory Activity in the Basal Ganglia-Thalamocortical
Network of the Hemiparkinsonian Rat
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE basal ganglia; beta oscillations; motor cortex; Parkinson's disease;
substantia nigra; ventral medial thalamus
ID EXTERNAL GLOBUS-PALLIDUS; LONG-TERM DEPRESSION; SUBTHALAMIC NUCLEUS;
PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; PATHOLOGICAL SYNCHRONIZATION;
VENTROMEDIAL NUCLEUS; EFFERENT CONNECTIONS; NEURONAL DISCHARGE;
MOVEMENT-DISORDERS
AB Loss of dopamine is associated with increased synchronization and oscillatory activity in the subthalamic nucleus and basal ganglia (BG) output nuclei in both Parkinson's disease (PD) patients and animal models of PD. We have previously observed substantial increases in spectral power in the 25-40 Hz range in LFPs recorded in the substantia nigra pars reticulata (SNpr) and motor cortex (MCx) in the hemiparkinsonian rat during treadmill walking. The current study explores the hypothesis that SNpr output entrains activity in the ventral medial thalamus (VM) in this frequency range after loss of dopamine, which in turn contributes to entrainment of the MCx and BG. Electrode bundles were implanted in MCx, SNpr, and VM of rats with unilateral dopamine cell lesions. Spiking and LFP activity were recorded during epochs of rest and walking on a circular treadmill. After dopamine cell lesion, 30 - 36 Hz LFP activity in the VM became more robust during treadmill walking and more coherent with LFP activity in the same range in MCx and SNpr. Infusion of the GABAA antagonist picrotoxin into the VM reduced both high beta power in MCx and SNpr and coherence between MCx and SNpr while temporarily restoring walking ability. Infusion of the GABAA agonist muscimol into the VM also reduced MCx-SNpr coherence and beta power but failed to improve walking. These results support the view that synchronized neuronal activity in the VM contributes to the emergence of high beta oscillations throughout the BG-thalamocortical network in the behaving parkinsonian rat.
C1 [Brazhnik, Elena; McCoy, Alex J.; Novikov, Nikolay; Hatch, Christina E.; Walters, Judith R.] NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35 Room 1C905, Bethesda, MD 20892 USA.
RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 35 Convent Dr,Bldg 35 Room 1C905, Bethesda, MD 20892 USA.
EM waltersj@ninds.nih.gov
FU Intramural Research Program of the National Institutes of
Health-National Institute of Neurological Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health-National Institute of Neurological
Disorders and Stroke. We thank Newlin Morgan, Tom Talbot, and Daryl
Brandy in the National Institute of Mental Health Section on
Instrumentation for design and fabrication of the rotary treadmill.
NR 62
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U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 13
PY 2016
VL 36
IS 15
BP 4196
EP 4208
DI 10.1523/JNEUROSCI.3582-15.2016
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DK7TX
UT WOS:000375129700007
PM 27076419
ER
PT J
AU Johnson, SP
Ramasawmy, R
Campbell-Washburn, AE
Wells, JA
Robson, M
Rajkumar, V
Lythgoe, MF
Pedley, RB
Walker-Samuel, S
AF Johnson, S. Peter
Ramasawmy, Rajiv
Campbell-Washburn, Adrienne E.
Wells, Jack A.
Robson, Mathew
Rajkumar, Vineeth
Lythgoe, Mark F.
Pedley, R. Barbara
Walker-Samuel, Simon
TI Acute changes in liver tumour perfusion measured non-invasively with
arterial spin labelling
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE perfusion; MRI; liver; cancer; metastasis; vascular disrupting agents
ID VASCULAR-DISRUPTING AGENT; COMBRETASTATIN A-4; SOLID TUMORS; MRI
MEASUREMENTS; NUDE-MICE; OXI4503; CANCER; COMBINATION; XENOGRAFTS;
ANTIBODY
AB Background: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503.
Methods: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R-2* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg(-1) OXi4503.
Results: A significant decrease in SW1222 tumour perfusion was observed (similar to 43 +/- 33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R-2* in LS174T tumours (28 +/- 25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits.
Conclusions: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting.
C1 [Johnson, S. Peter; Ramasawmy, Rajiv; Robson, Mathew; Rajkumar, Vineeth; Pedley, R. Barbara] UCL, Inst Canc, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England.
[Johnson, S. Peter; Ramasawmy, Rajiv; Campbell-Washburn, Adrienne E.; Wells, Jack A.; Lythgoe, Mark F.; Walker-Samuel, Simon] UCL, Ctr Adv Biomed Imaging, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England.
[Campbell-Washburn, Adrienne E.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Johnson, SP (reprint author), UCL, Inst Canc, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England.; Johnson, SP (reprint author), UCL, Ctr Adv Biomed Imaging, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England.
EM peter.johnson@cancer.ucl.ac.uk
OI Wells, Jack/0000-0002-4171-3539
FU MRC [MRC 1028351, MR/J013110/1]; Medical Research Funding DPFS grant
[MRC G100149]; National Centre for the Replacement, Reduction and
Refinement of Animal in Research [NC3Rs]; UK Regenerative Medicine
Platform Safety Hub [MRC: MR/K026739/1]; Wellcome Trust [WT100247MA];
Medical Research Council [42450]
FX We would like to thank OXiGENE (CA, USA) for kindly supplying the
vascular disrupting agent OXi4503. This work was carried out as part of
King's College London and UCL Comprehensive Cancer Imaging Centre,
Cancer Research UK & Engineering and Physical Sciences Research Council,
in association with the Medical Research Council (MRC), Department of
Health and British Heart Foundation (England) (C1519/A10331,
C1519/A16463). RR receives funding from the MRC (MRC 1028351). RBP
receives funding from Medical Research Funding DPFS grant (MRC G100149).
MFL receives funding from MRC (MR/J013110/1); the National Centre for
the Replacement, Reduction and Refinement of Animal in Research (NC3Rs);
UK Regenerative Medicine Platform Safety Hub (MRC: MR/K026739/1). SW-S
and SPJ receive funding from the Wellcome Trust (WT100247MA). JW
receives funding from the Medical Research Council (Grant code: 42450).
NR 35
TC 0
Z9 0
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD APR 13
PY 2016
VL 114
IS 8
BP 897
EP 904
DI 10.1038/bjc.2016.51
PG 8
WC Oncology
SC Oncology
GA DJ3TJ
UT WOS:000374129200007
PM 27031853
ER
PT J
AU Shchekotikhin, AE
Dezhenkova, LG
Tsvetkov, VB
Luzikov, YN
Volodina, YL
Tatarskiy, VV
Kalinina, AA
Treshalin, MI
Treshalina, HM
Romanenko, VI
Kaluzhny, DN
Kubbutat, M
Schols, D
Pommier, Y
Shtil, AA
Preobrazhenskaya, MN
AF Shchekotikhin, Andrey E.
Dezhenkova, Lyubov G.
Tsvetkov, Vladimir B.
Luzikov, Yuri N.
Volodina, Yulia L.
Tatarskiy, Victor V., Jr.
Kalinina, Anastasia A.
Treshalin, Michael I.
Treshalina, Helen M.
Romanenko, Vladimir I.
Kaluzhny, Dmitry N.
Kubbutat, Michael
Schols, Dominique
Pommier, Yves
Shtil, Alexander A.
Preobrazhenskaya, Maria N.
TI Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization
of synthesis and evaluation of antitumor properties
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Anthra[2,3-b]furan-3-carboxamides; DNA ligands; Topoisomerase
inhibitors; Protein kinase inhibitors; Cytotoxicity; Circumvention of
multidrug resistance; Antitumor activity
ID TOPOISOMERASE-I INHIBITORS; PROTEIN-KINASE CK2; CYTOTOXIC PROPERTIES;
CANCER CELLS; DNA; DOXORUBICIN; COMPLEXES; ANTHRACYCLINES;
IDENTIFICATION; INDUCTION
AB Anthraquinones and their analogues, in particular heteroarene-fused anthracendiones, are prospective scaffolds for new compounds with improved antitumor characteristics. We herein report the use of a 'scaffold hopping' approach for the replacement of the core structure in the previously discovered hit compound naphtho[2,3-f]indole-5,10-dione 2 with an alternative anthra[2,3-b]furan-5,10-dione scaffold. Among 13 newly synthesized derivatives the majority of 4,11-dihydroxy-2-methyl-5,10-dioxoanthra[2,3-b] furan-3-carboxamides demonstrated a high antiproliferative potency against a panel of wild type and drug resistant tumor cell lines, a property superior over the reference drug doxorubicin or lead naphtho[2,3-f] indole-5,10-dione 2. At low micromolar concentrations the selected derivative of (R)-3-aminopyrrolidine 3c and its stereoisomer (S)-3-aminopyrrolidine 3d caused an apoptotic cell death preceded by an arrest in the G2/M phase. Studies of intracellular targets showed that 3c and 3d formed stable intercalative complexes with the duplex DNA as determined by spectral analysis and molecular docking. Both 3c and 3d attenuated topoisomerase 1 and 2 mediated unwinding of the supercoiled DNA via a mechanism different from conventional DNA-enzyme tertiary complex formation. Furthermore, 3d decreased the activity of selected human protein kinases in vitro, indicating multiple targeting by the new chemotype. Finally, 3d demonstrated an antitumor activity in a model of murine intraperitoneally transplanted P388 leukemia, achieving the increase of animal life span up to 262% at tolerable doses. Altogether, the 'scaffold hopping' demonstrated its productivity for obtaining new perspective antitumor drug candidates. (C) 2016 Elsevier Masson SAS. All rights reserved.
C1 [Shchekotikhin, Andrey E.; Dezhenkova, Lyubov G.; Luzikov, Yuri N.; Treshalin, Michael I.; Shtil, Alexander A.; Preobrazhenskaya, Maria N.] Gause Inst New Antibiot, 11 B Pirogovskaya St, Moscow 119021, Russia.
[Shchekotikhin, Andrey E.] Mendeleyev Univ Chem Technol, 9 Miusskaya Sq, Moscow 125190, Russia.
[Tsvetkov, Vladimir B.] Russian Acad Sci, Topchiev Inst Petrochem Synth, 29 Leninsky Ave, Moscow 119991, Russia.
[Tsvetkov, Vladimir B.] Inst Phys Chem Med, 1A M Pirogovskaya St, Moscow 119435, Russia.
[Volodina, Yulia L.; Tatarskiy, Victor V., Jr.; Kalinina, Anastasia A.; Treshalina, Helen M.; Romanenko, Vladimir I.; Shtil, Alexander A.] Minist Hlth Russian Federat, NN Blokhin Canc Res Ctr, Fed State Budgetary Sci Inst, 24 Kashirskoye Shosse, Moscow 115478, Russia.
[Kaluzhny, Dmitry N.] Russian Acad Sci, Engelhardt Inst Mol Biol, 32 Vavilov St, Moscow 119991, Russia.
[Kubbutat, Michael] ProQinase GmbH, Breisacher Str 117, D-79106 Freiburg, Germany.
[Schols, Dominique] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Leuven, Belgium.
[Pommier, Yves] NCI, Dev Therapeut Branch, NIH, 37 Convent Dr,37-5068, Bethesda, MD 20892 USA.
RP Shchekotikhin, AE (reprint author), Gause Inst New Antibiot, 11 B Pirogovskaya St, Moscow 119021, Russia.
EM shchekotikhin@mail.ru
RI Tsvetkov, Vladimir/L-9399-2013; Kaluzhny, Dmitry/G-7256-2014
FU Ministry of Industry and Trade of the Russian Federation
[12411.1008799.13.007]
FX This study was supported by the Ministry of Industry and Trade of the
Russian Federation (state contract 12411.1008799.13.007).
NR 47
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Z9 4
U1 3
U2 19
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD APR 13
PY 2016
VL 112
BP 114
EP 129
DI 10.1016/j.ejmech.2016.01.050
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DH1PU
UT WOS:000372558200012
PM 26890118
ER
PT J
AU Cai, XY
Hu, YY
Tang, H
Hu, H
Pang, LJ
Xing, JY
Liu, ZY
Luo, YH
Jiang, B
Liu, T
Gorospe, M
Chen, C
Wang, WG
AF Cai, Xiaoyu
Hu, Yuanyuan
Tang, Hao
Hu, Han
Pang, Lijun
Xing, Junyue
Liu, Zhenyun
Luo, Yuhong
Jiang, Bin
Liu, Te
Gorospe, Myriam
Chen, Chuan
Wang, Wengong
TI RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence
SO ONCOTARGET
LA English
DT Article
DE NSUN2; SHC mRNA methylation; translational regulation; HUVEC; premature
senescence; Gerotarget
ID DELAYS REPLICATIVE SENESCENCE; 16S RIBOSOMAL-RNA; OXIDATIVE STRESS;
ESCHERICHIA-COLI; SIGNALING PATHWAY; LONGEVITY GENE; MESSENGER-RNA;
LIFE-SPAN; P66SHC; P66(SHC)
AB The tRNA methyltransferase NSUN2 delays replicative senescence by regulating the translation of CDK1 and CDKN1B mRNAs. However, whether NSUN2 influences premature cellular senescence remains untested. Here we show that NSUN2 methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC. Our results further show that the elevation of SHC expression by NSUN2-mediated mRNA methylation increased the levels of ROS, activated p38MAPK, thereby accelerating oxidative stress- and high-glucose-induced senescence of human vascular endothelial cells (HUVEC). Our findings highlight the critical impact of NSUN2-mediated mRNA methylation in promoting premature senescence.
C1 [Cai, Xiaoyu; Hu, Yuanyuan; Hu, Han; Pang, Lijun; Xing, Junyue; Liu, Zhenyun; Jiang, Bin; Wang, Wengong] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.
[Tang, Hao; Luo, Yuhong] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China.
[Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Liu, Te; Chen, Chuan] Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China.
RP Wang, WG (reprint author), Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.; Chen, C (reprint author), Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China.
EM ch9453@126.com; wwg@bjmu.edu.cn
FU National Science Foundation of China [81373706, 81230008, 81420108016,
91339114]; (111 project) from the Ministry of Education of People's
Republic of China [B07001]; NIA-IRP, NIH
FX This work was supported by Grants 81373706, 81230008, 81420108016, and
91339114 from the National Science Foundation of China; Grant B07001
(111 project) from the Ministry of Education of People's Republic of
China. M.G. was supported by the NIA-IRP, NIH.
NR 33
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 19099
EP 19110
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000003
PM 26992231
ER
PT J
AU Thanos, PK
Hamilton, J
O'Rourke, JR
Napoli, A
Febo, M
Volkow, ND
Blum, K
Gold, M
AF Thanos, Panayotis K.
Hamilton, John
O'Rourke, Joseph R.
Napoli, Anthony
Febo, Marcelo
Volkow, Nora D.
Blum, Kenneth
Gold, Mark
TI Dopamine D-2 gene expression interacts with environmental enrichment to
impact lifespan and behavior
SO ONCOTARGET
LA English
DT Article
DE aging; D-2; environmental enrichment; exercise; cognition; Gerotarget
ID REWARD DEFICIENCY SYNDROME; PREFRONTAL CORTEX; D2 RECEPTORS; BRAIN
DOPAMINE; LOCOMOTOR-ACTIVITY; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS;
WORKING-MEMORY; MICE; RAT
AB Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D-2 receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd(2) +/+), heterozygous (Drd(2) +/-) and knockout (Drd(2) -/-) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D-2 gene. Drd(2) +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd(2) +/+ and Drd(2) +/- EE mice lived 22% and 21% longer than Drd(2) -/- EE mice, respectively. Moreover, both body weight and locomotor activity were moderated by environmental factors. In addition, EE mice show greater behavioral variability between genotypes compared to DE mice with respect to body weight and locomotor activity.
C1 [Thanos, Panayotis K.; Hamilton, John; O'Rourke, Joseph R.] Univ Buffalo, Res Inst Addict, Behav Neuropharmacol & Neuroimaging Lab Addict, Buffalo, NY USA.
[Napoli, Anthony] Suffolk Community Coll, Dept Psychol, Riverhead, NY USA.
[Febo, Marcelo; Blum, Kenneth; Gold, Mark] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Thanos, PK (reprint author), Univ Buffalo, Res Inst Addict, Behav Neuropharmacol & Neuroimaging Lab Addict, Buffalo, NY USA.
EM pthanos@ria.buffalo.edu
RI Febo, Marcelo/G-5718-2011
FU Research Foundation of NY [RIAQ094]; NIH [AA 11034]
FX This work was supported by the Research Foundation of NY (RIAQ094) and
NIH (AA 11034).
NR 87
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Z9 0
U1 4
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 19111
EP 19123
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000004
PM 26992232
ER
PT J
AU Romashkan, SV
Das, SK
Villareal, DT
Ravussin, E
Redman, LM
Rochon, J
Bhapkar, M
Kraus, WE
AF Romashkan, Sergei V.
Das, Sai Krupa
Villareal, Dennis T.
Ravussin, Eric
Redman, Leanne M.
Rochon, James
Bhapkar, Manjushri
Kraus, William E.
CA CALERIE Study Grp
TI Safety of two-year caloric restriction in non-obese healthy individuals
SO ONCOTARGET
LA English
DT Article
DE calorie restriction; safety; humans; dietary energy restriction;
Gerotarget
ID BONE-MINERAL DENSITY; WEIGHT-LOSS; COMPREHENSIVE ASSESSMENT;
POSTMENOPAUSAL WOMEN; REDUCING INTAKE; CALERIE; SPAN; INTERVENTION;
DESIGN; ENERGY
AB Background: The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated.
Objective: Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults.
Design: A multi-center, randomized controlled trial. Participants were randomized using a 2: 1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored.
Results: Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal-weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group.
Conclusions: Two-years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important.
C1 [Romashkan, Sergei V.] NIA, Bethesda, MD 20892 USA.
[Das, Sai Krupa] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Boston, MA 02111 USA.
[Villareal, Dennis T.] Washington Univ, Sch Med, St Louis, MO USA.
[Villareal, Dennis T.] Baylor Coll Med, Houston, TX 77030 USA.
[Villareal, Dennis T.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Ravussin, Eric; Redman, Leanne M.] Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
[Rochon, James] Rho Fed Syst, Chapel Hill, NC USA.
[Rochon, James; Bhapkar, Manjushri; Kraus, William E.] Duke Clin Res Inst, Durham, NC USA.
[Rochon, James; Bhapkar, Manjushri; Kraus, William E.] Duke Univ, Sch Med, Durham, NC USA.
RP Das, SK (reprint author), Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Boston, MA 02111 USA.
EM sai.das@tufts.edu
FU National Institute on Aging (NIA); National Institute of Diabetes and
Kidney Diseases, National Institute of Health [U01AG022132, U01AG020478,
U01AG020487, U01AG020480]
FX This study was supported by the National Institute on Aging (NIA) and
National Institute of Diabetes and Kidney Diseases, National Institute
of Health (U01AG022132, U01AG020478, U01AG020487 and U01AG020480)
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PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 19124
EP 19133
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000005
PM 26992237
ER
PT J
AU Menard, C
Rezende, FA
Miloudi, K
Wilson, A
Tetreault, N
Hardy, P
SanGiovanni, JP
De Guire, V
Sapieha, P
AF Menard, Catherine
Rezende, Flavio A.
Miloudi, Khalil
Wilson, Ariel
Tetreault, Nicolas
Hardy, Pierre
SanGiovanni, John Paul
De Guire, Vincent
Sapieha, Przemyslaw
TI MicroRNA signatures in vitreous humour and plasma of patients with
exudative AMD
SO ONCOTARGET
LA English
DT Article
DE age-related macular degeneration; AMD; microRNAs; miRNA; biomarkers;
Gerotarget
ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; MESSENGER-RNAS;
CELLS; DISEASES; BIOMARKERS; RAPAMYCIN; INTERLEUKIN-1-BETA;
PROLIFERATION; ANGIOGENESIS
AB Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis.
C1 [Menard, Catherine; Tetreault, Nicolas; Sapieha, Przemyslaw] Univ Montreal, Dept Biochem, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H3C 3J7, Canada.
[Rezende, Flavio A.; Sapieha, Przemyslaw] Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.
[Wilson, Ariel] Ecole Polytech, Dept Engn Phys, Laser Proc & Plasmon Lab, Montreal, PQ H3C 3A7, Canada.
[Miloudi, Khalil; Sapieha, Przemyslaw] McGill Univ, Dept Neurosci, Montreal, PQ, Canada.
[Hardy, Pierre] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada.
[Hardy, Pierre] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada.
[SanGiovanni, John Paul] NIAAA, Lab Membrane Biochem & Biophys, Nutr Neurosci Sect, NIH, Bethesda, MD USA.
[De Guire, Vincent] Hop Maison Neuve Rosemont, Dept Clin Biochem, Quebec City, PQ, Canada.
RP Sapieha, P (reprint author), Univ Montreal, Dept Biochem, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H3C 3J7, Canada.; Sapieha, P (reprint author), Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Dept Ophthalmol, Montreal, PQ, Canada.; Sapieha, P (reprint author), McGill Univ, Dept Neurosci, Montreal, PQ, Canada.; De Guire, V (reprint author), Hop Maison Neuve Rosemont, Dept Clin Biochem, Quebec City, PQ, Canada.
EM vdeguire.hmr@ssss.gouv.qc.ca; mike.sapieha@umontreal.ca
FU Foundation Fighting Blindness Canada; Canadian Institutes of Health
Research [221478]; Natural Sciences and Engineering Research Council of
Canada [418637]; Fondation HMR; Reseau en Recherche en Sante de la
Vision du Quebec; Fond en Recherche en Opthalmologie de l'UdeM
FX PS holds a Canada Research Chair in Retinal Cell Biology and The Alcon
Research Institute Young Investigator Award. This work was supported by
operating grants to PS from the Foundation Fighting Blindness Canada and
the Canadian Institutes of Health Research (221478) and Natural Sciences
and Engineering Research Council of Canada (418637). Additional support
was obtained from the Fondation HMR, Reseau en Recherche en Sante de la
Vision du Quebec and the Fond en Recherche en Opthalmologie de l'UdeM.
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PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 19171
EP 19184
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000008
PM 27015561
ER
PT J
AU Liu, F
Zhang, SM
Zhao, Z
Mao, XR
Huang, JL
Wu, ZX
Zheng, L
Wang, Q
AF Liu, Fei
Zhang, Shimeng
Zhao, Zhen
Mao, Xinru
Huang, Jinlan
Wu, Zixian
Zheng, Lei
Wang, Qian
TI MicroRNA-27b up-regulated by human papillomavirus 16 E7 promotes
proliferation and suppresses apoptosis by targeting polo-like kinase2 in
cervical cancer
SO ONCOTARGET
LA English
DT Article
DE microRNA-27b; HPV16 E7; cervical cancer; polo-like kinase2; DGCR8
ID TUMOR-SUPPRESSOR; CELL-GROWTH; EXPRESSION; LINES
AB The infection with high-risk human papillomavirus is linked to cervical cancer, nevertheless, the role of miRNAs regulated by HPV oncogenes in cancer progression remain largely unknown. Here, we knocked down endogenous E6/E7 in HPV16-positive CaSki cell lines, screened differences in miRNA expression profile with control using miRNA array. 38 miRNAs were down-regulated and 6 miRNAs were up-regulated in the E6/E7 silenced CaSki cells (> 2-fold changes with P < 0.05). The levels of miR-27b, miR-20a, miR-24, miR-93, and miR-106b were verified by qPCR in E6/E7 silenced CaSki and SiHa cells. MiR-27b, up-regulated by E7, promoted CaSki and SiHa cell proliferation and invasion, inhibit paclitaxel-induced apoptosis. Dual-luciferase experiment confirmed miR-27b down-regulated its target gene PLK2 through the "seed regions". The tumor suppressor PLK2 inhibited SiHa cell proliferation, reduced cell viability, and promoted paclitaxel/cisplatin -induced apoptosis. Furthermore, DGCR8 was found to mediate the up-regulation of miR-27b by HPV16 E7. Our study demonstrated that HPV16 E7 could increase DGCR8 to promote the generation of miR-27b, which accelerated cell proliferation and inhibited paclitaxel-induced cell apoptosis through down-regulating PLK2. These findings provide an insight into the interaction network of viral oncogene, miR-27b and PLK2, and support the potential strategies using antisense nucleic acid of miR-27b for therapy of cervical cancer in the future.
C1 [Liu, Fei; Zhang, Shimeng; Mao, Xinru; Huang, Jinlan; Wu, Zixian; Zheng, Lei; Wang, Qian] Southern Med Univ, Nanfang Hosp, Dept Lab Med, Guangzhou 510515, Guangdong, Peoples R China.
[Liu, Fei] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Clin Lab, Guangzhou 510623, Guangdong, Peoples R China.
[Zhang, Shimeng] Shenzhen Shekou Peoples Hosp, Cent Lab, Shenzhen 518000, Peoples R China.
[Zhao, Zhen] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Zheng, L; Wang, Q (reprint author), Southern Med Univ, Nanfang Hosp, Dept Lab Med, Guangzhou 510515, Guangdong, Peoples R China.
EM nfyyzhenglei@smu.edu.cn; wangqian@smu.edu.cn
FU National Natural Science Foundation of China [81371901]; Specialized
Research Fund for the Doctoral Program of Higher Education of China
[20134433110010]; Intramural Research Programs of the Clinical Center of
the National Institutes of Health; CPOCT grant American Association of
Clinical Chemistry (A new electrochemical biosensor for circulating
microRNA); Science and Technology Innovation Cultivation Project of
Guangdong Undergraduate Students [pdjh2015b0116]; National Undergraduate
Training Programs for Innovation and Entrepreneurship [201512121031]
FX We thank Professor Chunlin Chen (Department of Gynecology and
Obstetrics, Nanfang Hospital, Southern Medical University) to provide
cervical cancer tissue samples. This research was supported by the
National Natural Science Foundation of China (NO. 81371901), Specialized
Research Fund for the Doctoral Program of Higher Education of China
(NO.20134433110010), Intramural Research Programs of the Clinical Center
of the National Institutes of Health (ZZ) and CPOCT grant American
Association of Clinical Chemistry (A new electrochemical biosensor for
circulating microRNA). Science and Technology Innovation Cultivation
Project of Guangdong Undergraduate Students (pdjh2015b0116), National
Undergraduate Training Programs for Innovation and Entrepreneurship
(201512121031).
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PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 19666
EP 19679
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000045
PM 26910911
ER
PT J
AU Zhu, Z
Pang, BX
Iglesias-Bartolome, R
Wu, XS
Hu, L
Zhang, CM
Wang, JS
Gutkind, JS
Wang, SL
AF Zhu, Zhao
Pang, Baoxing
Iglesias-Bartolome, Ramiro
Wu, Xiaoshan
Hu, Lei
Zhang, Chunmei
Wang, Jinsong
Gutkind, J. Silvio
Wang, Songlin
TI Prevention of irradiation-induced salivary hypofunction by rapamycin in
swine parotid glands
SO ONCOTARGET
LA English
DT Article
DE radiotherapy; salivary hypofunction; miniature pig; rapamycin; mTOR
ID HUMAN AQUAPORIN-1 CDNA; MINIATURE PIG; SUBMANDIBULAR-GLAND;
CLINICAL-ONCOLOGY; INDUCED MUCOSITIS; AMERICAN-SOCIETY; NECK
IRRADIATION; FLUID SECRETION; CANCER-PATIENTS; MOUSE MODEL
AB Radiotherapy is commonly used in patients with oral cavity and pharyngeal cancers, usually resulting in irreversible salivary hypofunction. Currently management of radiation damage to salivary glands still remains a great challenge. Recent studies show that activation of mammalian target of rapamycin (mTOR) occurs in salivary gland lesions, making it possible to apply mTOR inhibitor for treatment. Our results indicate inhibition of mTOR by rapamycin significantly alleviated irradiation-induced salivary hypofunction by restoring 46% salivary flow rate and protecting histological structures in swine. Furthermore, rapamycin protected human submandibular gland cell line (HSG) from irradiation-induced cell depletion and loss of cell proliferation capacity. These findings lay the foundation for a new clinical application of rapamycin to prevent irradiation-induced salivary hypofunction.
C1 [Zhu, Zhao; Pang, Baoxing; Wu, Xiaoshan; Hu, Lei; Zhang, Chunmei; Wang, Jinsong; Wang, Songlin] Capital Med Univ, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Sch Stomatol, Beijing 100050, Peoples R China.
[Iglesias-Bartolome, Ramiro] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20852 USA.
[Gutkind, J. Silvio] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Gutkind, J. Silvio] Moores Canc Ctr, La Jolla, CA 92093 USA.
RP Wang, SL (reprint author), Capital Med Univ, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Sch Stomatol, Beijing 100050, Peoples R China.; Gutkind, JS (reprint author), Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.; Gutkind, JS (reprint author), Moores Canc Ctr, La Jolla, CA 92093 USA.
EM sgutkind@ucsd.edu; slwang@ccmu.edu.cn
FU Beijing Municipality Government grants (Beijing Scholar Program)
[PXM2014_014226_000180, PXM2014_014226_000048, PXM2014_014226_000013,
PXM2014_014226_000053, Z121100005212004, PXM2013_014226_000021,
PXM2013_014226_07_000080, TJSHG201310025005]; National Basic Research
Program of China [2010CB944801]
FX This work was supported by a grant from the Beijing Municipality
Government grants (Beijing Scholar Program-PXM2014_014226_000180,
PXM2014_014226_000048, PXM2014_014226_000013, PXM2014_014226_000053,
Z121100005212004, PXM2013_014226_000021, PXM2013_014226_07_000080, and
TJSHG201310025005 to S.W.), the National Basic Research Program of China
(2010CB944801 to S.W.)
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U1 2
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 20271
EP 20281
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000089
PM 26958808
ER
PT J
AU Guo, ZJ
Yang, L
Qian, F
Wang, YX
Yu, X
Ji, CD
Cui, W
Xiang, DF
Zhang, X
Zhang, P
Wang, JM
Cui, YH
Bian, XW
AF Guo, Zheng-Jun
Yang, Lang
Qian, Feng
Wang, Yan-Xia
Yu, Xi
Ji, Cheng-Dong
Cui, Wei
Xiang, Dong-Fang
Zhang, Xia
Zhang, Peng
Wang, Ji Ming
Cui, You-Hong
Bian, Xiu-Wu
TI Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to
promote invasive and metastatic potentials of human gastric cancer
SO ONCOTARGET
LA English
DT Article
DE RUNX2; gastric cancer; invasion; metastasis; CXCR4
ID STEM-CELLS; OSTEOBLAST DIFFERENTIATION; EXPRESSION; FAMILY; GENE;
IDENTIFICATION; TRAFFICKING; ASSOCIATION; SUPPRESSOR; CARCINOMA
AB Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC.
C1 [Guo, Zheng-Jun; Yang, Lang; Wang, Yan-Xia; Yu, Xi; Ji, Cheng-Dong; Cui, Wei; Xiang, Dong-Fang; Zhang, Xia; Zhang, Peng; Cui, You-Hong; Bian, Xiu-Wu] Third Mil Med Univ, Inst Pathol, Minist Educ China, Chongqing, Peoples R China.
[Guo, Zheng-Jun; Yang, Lang; Wang, Yan-Xia; Yu, Xi; Ji, Cheng-Dong; Cui, Wei; Xiang, Dong-Fang; Zhang, Xia; Zhang, Peng; Cui, You-Hong; Bian, Xiu-Wu] Third Mil Med Univ, Southwest Canc Ctr, Minist Educ China, Chongqing, Peoples R China.
[Guo, Zheng-Jun; Yang, Lang; Wang, Yan-Xia; Yu, Xi; Ji, Cheng-Dong; Cui, Wei; Xiang, Dong-Fang; Zhang, Xia; Zhang, Peng; Cui, You-Hong; Bian, Xiu-Wu] Third Mil Med Univ, Key Lab Tumor Immunopathol, Minist Educ China, Chongqing, Peoples R China.
[Qian, Feng] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing, Peoples R China.
[Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Bian, Xiu-Wu] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China.
RP Cui, YH; Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Minist Educ China, Chongqing, Peoples R China.; Cui, YH; Bian, XW (reprint author), Third Mil Med Univ, Southwest Canc Ctr, Minist Educ China, Chongqing, Peoples R China.; Cui, YH; Bian, XW (reprint author), Third Mil Med Univ, Key Lab Tumor Immunopathol, Minist Educ China, Chongqing, Peoples R China.; Bian, XW (reprint author), Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China.
EM cuiyouhongx@yahoo.com; bianxiuwu@263.net
RI Bian, Xiu-wu/D-4736-2017; Zhang, Xia/B-8152-2008
OI Bian, Xiu-wu/0000-0003-4383-0197; Zhang, Xia/0000-0002-9040-1486
FU National Natural Science Foundation of China (NSFC) [81230062, 81071771,
81372555]; Federal funds from the National Cancer Institute (NCI),
National Institutes of Health (NIH) [HHSN261200800001E]; Intramural
Research Program of the NCI, NIH
FX This work was supported by grants from the National Natural Science
Foundation of China (NSFC Nos. 81230062, 81071771 and 81372555). JMW has
been funded in part with Federal funds from the National Cancer
Institute (NCI), National Institutes of Health (NIH), under Contract No.
HHSN261200800001E as well as supported in part by the Intramural
Research Program of the NCI, NIH.
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PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 12
PY 2016
VL 7
IS 15
BP 20999
EP 21012
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL7ES
UT WOS:000375804000143
PM 27007162
ER
PT J
AU Cheung, KH
Keerthikumar, S
Roncaglia, P
Subramanian, SL
Roth, ME
Samuel, M
Anand, S
Gangoda, L
Gould, S
Alexander, R
Galas, D
Gerstein, MB
Hill, AF
Kitchen, RR
Lotvall, J
Patel, T
Procaccini, DC
Quesenberry, P
Rozowsky, J
Raffai, RL
Shypitsyna, A
Su, AI
Thery, C
Vickers, K
Wauben, MHM
Mathivanan, S
Milosavljevic, A
Laurent, LC
AF Cheung, Kei-Hoi
Keerthikumar, Shivakumar
Roncaglia, Paola
Subramanian, Sai Lakshmi
Roth, Matthew E.
Samuel, Monisha
Anand, Sushma
Gangoda, Lahiru
Gould, Stephen
Alexander, Roger
Galas, David
Gerstein, Mark B.
Hill, Andrew F.
Kitchen, Robert R.
Lotvall, Jan
Patel, Tushar
Procaccini, Dena C.
Quesenberry, Peter
Rozowsky, Joel
Raffai, Robert L.
Shypitsyna, Aleksandra
Su, Andrew I.
Thery, Clotilde
Vickers, Kasey
Wauben, Marca H. M.
Mathivanan, Suresh
Milosavljevic, Aleksandar
Laurent, Louise C.
TI Extending gene ontology in the context of extracellular RNA and vesicle
communication
SO JOURNAL OF BIOMEDICAL SEMANTICS
LA English
DT Article
DE Ontology; Extracellular RNA; Extracellular vesicle; Metadata; Faceted
search; Atlas
ID VIRUS-LIKE PARTICLES; HUMAN PLASMA; MEDIATED TRANSFER; MICRORNAS;
PROTEINS; EXOSOMES; CANCER; CELLS; TOOL; IDENTIFICATION
AB Background: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research.
Methods: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations.
Results: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO.
Conclusions: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
C1 [Cheung, Kei-Hoi] Yale Univ, Sch Med, Dept Emergency Med, Yale Ctr Med Informat, New Haven, CT USA.
[Cheung, Kei-Hoi] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Keerthikumar, Shivakumar; Samuel, Monisha; Anand, Sushma; Gangoda, Lahiru; Hill, Andrew F.; Mathivanan, Suresh] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic 3086, Australia.
[Roncaglia, Paola; Shypitsyna, Aleksandra] European Mol Biol Lab, European Bioinformat Inst EMBL EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
[Subramanian, Sai Lakshmi; Roth, Matthew E.; Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Bioinformat Res Lab, Houston, TX 77030 USA.
[Gould, Stephen] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Alexander, Roger; Galas, David] Pacific Northwest Diabet Res Inst, Seattle, WA USA.
[Gerstein, Mark B.; Kitchen, Robert R.; Rozowsky, Joel] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA.
[Gerstein, Mark B.] Yale Univ, Dept Comp Sci, POB 2158, New Haven, CT 06520 USA.
[Gerstein, Mark B.; Rozowsky, Joel] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA.
[Lotvall, Jan] Univ Gothenburg, Gothenburg, Sweden.
[Patel, Tushar] Mayo Clin Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
[Procaccini, Dena C.] NIDA, Div Neurosci & Behav, Rockville, MD USA.
[Quesenberry, Peter] Univ Med Comprehens Canc Ctr, Providence, RI USA.
[Raffai, Robert L.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Raffai, Robert L.] VA Med Ctr, San Francisco, CA USA.
[Su, Andrew I.] Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA.
[Thery, Clotilde] PSL Res Univ, Inst Curie, INSERM, U932, Paris, France.
[Vickers, Kasey] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Wauben, Marca H. M.] Univ Utrecht, Dept Biochem & Cell Biol, Utrecht, Netherlands.
[Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA.
RP Cheung, KH (reprint author), Yale Univ, Sch Med, Dept Emergency Med, Yale Ctr Med Informat, New Haven, CT USA.; Laurent, LC (reprint author), Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA.
EM kei.cheung@yale.edu; llaurent@ucsd.edu
RI Mathivanan, Suresh/D-2045-2009; KEERTHIKUMAR, SHIVAKUMAR/B-4673-2011;
thery, clotilde/F-6373-2013;
OI Mathivanan, Suresh/0000-0002-7290-5795; KEERTHIKUMAR,
SHIVAKUMAR/0000-0001-9865-9767; thery, clotilde/0000-0001-8294-6884;
Roncaglia, Paola/0000-0002-2825-0621; Rozowsky, Joel/0000-0002-3565-0762
FU NIH Common Fund, through the Office of Strategic Coordination; NIH
Common Fund, through the Office of the NIH Director [U54DA036134,
UH2TR000906, U01HL126494, UH3TR000884, U19CA179512]; Gene Ontology
Consortium (P41 grant from the National Human Genome Research Institute
(NHGRI)) [5U41HG002273-14]; European Molecular Biology Laboratory (EMBL)
FX This work was supported in part by the NIH Common Fund, through the
Office of Strategic Coordination and the Office of the NIH Director (AM:
U54DA036134, LCL: UH2TR000906 and U01HL126494, TP: UH3TR000884, and RR:
U19CA179512). Paola Roncaglia and Aleksandra Shypitsyna are funded by
the Gene Ontology Consortium (P41 grant from the National Human Genome
Research Institute (NHGRI), grant 5U41HG002273-14). Aleksandra
Shypitsyna is also funded from the European Molecular Biology Laboratory
(EMBL). We would like to give special thanks to Dena C. Procaccini for
coordinating meetings and conference calls facilitating discussion and
collaboration as part of the manuscript writing. We would like to thank
Tony Sawford (Protein Function Development team, EMBL-EBI) for running
the set of ExoCarta and Vesiclepedia annotations through the validation
pipeline for inclusion in the GOA database. We would also like to thank
Xandra O. Breakefield for her insights and comments. Finally we would
like to acknowledge the community support offered by the following
Consortiums: Extracellular RNA Communication (ERC) Consortium, Gene
Ontology Consortium (GOC), and International Society for Extracellular
Vesicles (ISEV), and American Society for Exosomes and Microvesicles
(ASEMV).
NR 50
TC 3
Z9 3
U1 10
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2041-1480
J9 J BIOMED SEMANT
JI J. Biomed. Semant.
PD APR 12
PY 2016
VL 7
AR UNSP 19
DI 10.1186/s13326-016-0061-5
PG 9
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DK4ZD
UT WOS:000374928000002
PM 27076901
ER
PT J
AU Ramsden, CE
Zamora, D
Majchrzak-Hong, S
Faurot, KR
Broste, SK
Frantz, RP
Davis, JM
Ringel, A
Suchindran, CM
Hibbeln, JR
AF Ramsden, Christopher E.
Zamora, Daisy
Majchrzak-Hong, Sharon
Faurot, Keturah R.
Broste, Steven K.
Frantz, Robert P.
Davis, John M.
Ringel, Amit
Suchindran, Chirayath M.
Hibbeln, Joseph R.
TI Re-evaluation of the traditional diet-heart hypothesis: analysis of
recovered data from Minnesota Coronary Experiment (1968-73)
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID LINOLEIC-ACID METABOLITES; ESTROGEN REPLACEMENT THERAPY; SERUM
CHOLESTEROL RESPONSE; LOW-DENSITY LIPOPROTEINS; FATTY LIVER-DISEASE;
CLINICAL-TRIAL DATA; SECONDARY PREVENTION; METAANALYSIS; LIPIDS; RISK
AB OBJECTIVE
To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis.
DESIGN
The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted.
SETTING
One nursing home and six state mental hospitals in Minnesota, United States.
PARTICIPANTS
Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files.
INTERVENTIONS
Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings.
MAIN OUTCOME MEASURES
Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. RESULTS The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline -13.8% v -1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n= 10 808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27).
CONCLUSIONS
Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.
C1 [Ramsden, Christopher E.; Majchrzak-Hong, Sharon; Ringel, Amit; Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Ramsden, Christopher E.; Faurot, Keturah R.] Univ N Carolina, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC USA.
[Zamora, Daisy; Davis, John M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Broste, Steven K.] Medtronic, Minneapolis, MN USA.
[Frantz, Robert P.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Davis, John M.] Univ Illinois, Inst Psychiat, Chicago, IL USA.
[Suchindran, Chirayath M.] UNC Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
RP Ramsden, CE (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.; Ramsden, CE (reprint author), Univ N Carolina, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC USA.
EM Chris.Ramsden@nih.gov
FU US Public Health Service; National Heart Institute through R01 mechanism
[HE09686]; intramural program of the National Institute on Alcohol Abuse
and Alcoholism, National Institutes of Health; University of North
Carolina Program on Integrative Medicine (National Institutes of Health)
[T-32 AT003378]
FX The MCE was funded by the US Public Health Service and the National
Heart Institute through the R01 mechanism (grant HE09686). The
intramural program of the National Institute on Alcohol Abuse and
Alcoholism, National Institutes of Health, and the University of North
Carolina Program on Integrative Medicine (National Institutes of Health
grant T-32 AT003378) supported data recovery and evaluation. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health or the
US Public Health Service.
NR 78
TC 3
Z9 4
U1 5
U2 15
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD APR 12
PY 2016
VL 353
AR i1246
DI 10.1136/bmj.i1246
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ7ER
UT WOS:000374375200001
PM 27071971
ER
PT J
AU Fu, G
Ding, Y
Seal, A
Chen, B
Sun, YZ
Bolton, E
AF Fu, Gang
Ding, Ying
Seal, Abhik
Chen, Bin
Sun, Yizhou
Bolton, Evan
TI Predicting drug target interactions using meta-path-based semantic
network analysis
SO BMC BIOINFORMATICS
LA English
DT Article
DE Semantic network analysis; Link prediction; Meta-path topological
feature; Machine learning; Random forest
ID SYSTEMS CHEMICAL BIOLOGY; DISCOVERY; PUBCHEM; DATABASES; FRAMEWORK;
SUBSTANCE; COMPOUND
AB Background: In the context of drug discovery, drug target interactions (DTIs) can be predicted based on observed topological features of a semantic network across the chemical and biological space. In a semantic network, the types of the nodes and links are different. In order to take into account the heterogeneity of the semantic network, meta-path-based topological patterns were investigated for link prediction.
Results: Supervised machine learning models were constructed based on meta-path topological features of an enriched semantic network, which was derived from Chem2Bio2RDF, and was expanded by adding compound and protein similarity neighboring links obtained from the PubChem databases. The additional semantic links significantly improved the predictive performance of the supervised learning models. The binary classification model built upon the enriched feature space using the Random Forest algorithm significantly outperformed an existing semantic link prediction algorithm, Semantic Link Association Prediction (SLAP), to predict unknown links between compounds and protein targets in an evolving network. In addition to link prediction, Random Forest also has an intrinsic feature ranking algorithm, which can be used to select the important topological features that contribute to link prediction.
Conclusions: The proposed framework has been demonstrated as a powerful alternative to SLAP in order to predict DTIs using the semantic network that integrates chemical, pharmacological, genomic, biological, functional, and biomedical information into a unified framework. It offers the flexibility to enrich the feature space by using different normalization processes on the topological features, and it can perform model construction and feature selection at the same time.
C1 [Fu, Gang; Bolton, Evan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD USA.
[Ding, Ying; Seal, Abhik] Indiana Univ, Sch Informat & Comp, 107 S Indiana Ave, Bloomington, IN USA.
[Ding, Ying] Wuhan Univ, Sch Informat Management, Wuhan 430072, Hubei, Peoples R China.
[Chen, Bin] Stanford Univ, Dept Med, 450 Serra Mall, Stanford, CA 94305 USA.
[Sun, Yizhou] Northeastern Univ, Coll Comp & Informat Sci, 360 Huntington Ave, Boston, MA 02115 USA.
RP Fu, G (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD USA.
EM gang.fu@nih.gov
FU Intramural Research Program of the National Library of Medicine, NIH
FX This research was supported [in part] by the Intramural Research Program
of the National Library of Medicine, NIH. Many thanks to the PubChem
team, who provided database API functions to retrieve data from Compound
and BioAssay databases. Many thanks to Ming Hao in the discussion about
R packages and calculations. Many thanks to Jeremy Yang in the
discussion and help to maintain Chem2Bio2RDF web server.
NR 31
TC 2
Z9 2
U1 14
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD APR 12
PY 2016
VL 17
AR 160
DI 10.1186/s12859-016-1005-x
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DJ5VX
UT WOS:000374280000001
PM 27071755
ER
PT J
AU Lee, P
Bova, R
Schofield, L
Bryant, W
Dieckmann, W
Slattery, A
Govendir, MA
Emmett, L
Greenfield, JR
AF Lee, Paul
Bova, Ron
Schofield, Lynne
Bryant, Wendy
Dieckmann, William
Slattery, Anthony
Govendir, Matt A.
Emmett, Louise
Greenfield, Jerry R.
TI Brown Adipose Tissue Exhibits a Glucose-Responsive Thermogenic Biorhythm
in Humans
SO CELL METABOLISM
LA English
DT Article
ID BETA-ADRENERGIC STIMULATION; ADULT HUMANS; MESSENGER-RNA; COLD-EXPOSURE;
ADIPOCYTES; INSULIN; FAT; METABOLISM; ACTIVATION; HEAT
AB High abundance of brown adipose tissue (BAT) is linked to lower glycaemia in humans, leading to the belief that BAT may protect against diabetes. The relationship between BAT glucose utilization and systemic glucose homeostasis has not been defined. In this paper we have characterized glycaemic excursions and BAT thermogenic responses in human brown adipocytes, BAT explants, and healthy adults through supraclavicular temperature profiling, revealing their circadian coupling in vivo and in vitro, orchestrated by UCP1, GLUT4, and Rev-erb alpha biorhythms. Extent of glycated haemoglobin also correlated positively with environmental temperature among community-dwelling patients. These data uncover potential crosstalk between BAT and glucose regulatory pathways, evident on cellular, tissue, individual, and population levels, and provide impetus to search for BAT harnessing strategies for therapeutic purposes.
C1 [Lee, Paul; Schofield, Lynne; Govendir, Matt A.; Greenfield, Jerry R.] Garvan Inst Med Res, Diabet & Metab Div, Sydney, NSW 2010, Australia.
[Lee, Paul; Schofield, Lynne; Greenfield, Jerry R.] St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia.
[Bova, Ron] St Vincents Hosp, Dept Surg, Sydney, NSW 2010, Australia.
[Slattery, Anthony; Emmett, Louise] St Vincents Hosp, Dept PET & Nucl Med, Sydney, NSW 2010, Australia.
[Bryant, Wendy; Greenfield, Jerry R.] St Vincents Hosp, Ctr Diabet, Sydney, NSW 2010, Australia.
[Dieckmann, William] NIH, Dept Positron Emiss Tomog, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Paul; Greenfield, Jerry R.] Univ New S Wales, Fac Med, Sydney, NSW 2052, Australia.
RP Lee, P (reprint author), Garvan Inst Med Res, Diabet & Metab Div, Sydney, NSW 2010, Australia.; Lee, P (reprint author), St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia.; Lee, P (reprint author), Univ New S Wales, Fac Med, Sydney, NSW 2052, Australia.
EM p.lee@garvan.org.au
FU Australian National Health Medical Research Council (NHMRC)
[APP1035997]; NHMRC, Australia [APP1088123]; Diabetes Australia Research
Trust (DART) Grant; Royal Australasian College of Physicians (RACP)
Foundations Establishment Fellowship; Ramaciotti Establishment
Fellowship
FX P.L. was supported by an Australian National Health Medical Research
Council (NHMRC) Early Career Fellowship (APP1035997). This study was
supported by Project Grant (APP1088123) NHMRC, Australia, Diabetes
Australia Research Trust (DART) Grant, the Royal Australasian College of
Physicians (RACP) Foundations Establishment Fellowship and Ramaciotti
Establishment Fellowship. The authors thank Professor Don Chisholm for
helpful discussions and Ms. Samarina Musaad from LabTests New Zealand
for provision of glycated haemoglobin data.
NR 24
TC 9
Z9 12
U1 5
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD APR 12
PY 2016
VL 23
IS 4
BP 602
EP 609
DI 10.1016/j.cmet.2016.02.007
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DJ3RL
UT WOS:000374123200009
PM 26972823
ER
PT J
AU Xu, BB
Luo, ZP
Gao, WX
Wilson, AJ
He, C
Chen, X
Yuan, GL
Dai, HL
Rao, Y
Willets, K
Dauter, Z
Ren, SQ
AF Xu, Beibei
Luo, Zhipu
Gao, Wenxiu
Wilson, Andrew J.
He, Chao
Chen, Xing
Yuan, Guoliang
Dai, Hai-Lung
Rao, Yi
Willets, Katherine
Dauter, Zbigniew
Ren, Shenqiang
TI Solution-Processed Molecular Opto-Ferroic Crystals
SO CHEMISTRY OF MATERIALS
LA English
DT Article
ID ORGANIC SEMICONDUCTING MATERIALS; CHARGE-TRANSFER INTERFACES;
FIELD-EFFECT TRANSISTORS; TRANSFER COMPLEXES; MOTT INSULATOR; TRANSFER
SALT; C-60; MULTIFERROICS; MAGNETISM; FERROELECTRICITY
AB Supramolecular assembly utilizing noncovalent interaction to construct ordered molecular charge-transfer solids has led to significant advancement and breakthrough in energy-efficient molecular electronics, memories and solar cells. However, to exploit the coupling across these different energy regimes, the method that is capable of manipulating charge-spinlattice interactions is indispensable. Here, by rational chemical design of the supramolecular assembled charge-transfer networks, opto-ferroic properties can be coupled, in which a collective electron transfer and ordering strongly influence the dipole and spin orders, as well as their coupling. The supramolecular charge-transfer crystal presented here opens up a new route for the development of multifunctional organics that can lead to significant advancement in molecular ferronics.
C1 [Xu, Beibei; Ren, Shenqiang] Temple Univ, Dept Mech Engn, Philadelphia, PA 19122 USA.
[Xu, Beibei; Ren, Shenqiang] Temple Univ, Temple Mat Inst, Philadelphia, PA 19122 USA.
[Luo, Zhipu; Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, NCI, 9700 S Cass Ave, Argonne, IL 60439 USA.
[Gao, Wenxiu; Yuan, Guoliang] Nanjing Univ Sci & Technol, Sch Mat Sci & Engn, Nanjing 210094, Jiangsu, Peoples R China.
[Wilson, Andrew J.; He, Chao; Dai, Hai-Lung; Rao, Yi; Willets, Katherine] Temple Univ, Dept Chem, Philadelphia, PA 19122 USA.
[He, Chao] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
[He, Chao] Univ Sci & Technol China, Dept Chem Phys, Hefei 230026, Anhui, Peoples R China.
[Chen, Xing] Argonne Natl Lab, Div Energy Syst, Argonne, IL 60439 USA.
RP Ren, SQ (reprint author), Temple Univ, Dept Mech Engn, Philadelphia, PA 19122 USA.; Ren, SQ (reprint author), Temple Univ, Temple Mat Inst, Philadelphia, PA 19122 USA.
EM shenqiang.ren@temple.edu
OI Wilson, Andrew/0000-0003-3427-810X
FU Army Research Office - Young Investigator Program [W911NF-15-1-0610];
U.S. Department of Energy-Basic Energy Sciences [DE-SC0014902];
Department of Energy (DOE), Office of Science, Basic Energy Science
(BES) [DE-SC0010307]; Energy Frontier Research Center at Temple
University - U.S. Department of Energy, Office of Science, Basic Energy
Sciences [DE-SC0012575]; Targeted Research Grant from Temple University
Office of the Vice Provost for Research; U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX Work at Temple University (S.R) was supported by the Army Research
Office - Young Investigator Program (W911NF-15-1-0610, material
design/self-assembly of carbon photovoltaics), U.S. Department of
Energy-Basic Energy Sciences Award No. DE-SC0014902 (organic synthesis
and physical property measurement). Work at Temple University (A.W. and
K.W.) was supported by the Department of Energy (DOE), Office of
Science, Basic Energy Science (BES) under Award #DE-SC0010307. Y.R and
H.L.D acknowledge the seed funding from an Energy Frontier Research
Center at Temple University funded by the U.S. Department of Energy,
Office of Science, Basic Energy Sciences under Award # DE-SC0012575, a
Targeted Research Grant from the Temple University Office of the Vice
Provost for Research. Diffraction data were collected at the SER-CAT
beamline 22BM at the Advanced Photon Source, Argonne National
Laboratory. Use of the Advanced Photon Source was supported by the U.S.
Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-31-109-Eng-38. The authors thank Temple
Materials Institute and Prof. X. Xi for the AFM measurements. The
authors also thank X. Chen at University of Maryland for the dielectric
measurements.
NR 49
TC 3
Z9 3
U1 7
U2 28
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0897-4756
EI 1520-5002
J9 CHEM MATER
JI Chem. Mat.
PD APR 12
PY 2016
VL 28
IS 7
BP 2441
EP 2448
DI 10.1021/acs.chemmater.6b00836
PG 8
WC Chemistry, Physical; Materials Science, Multidisciplinary
SC Chemistry; Materials Science
GA DJ4RS
UT WOS:000374196000060
ER
PT J
AU Sansone, VA
Burge, J
McDermott, MP
Smith, PC
Herr, B
Tawil, R
Pandya, S
Kissel, J
Ciafaloni, E
Shieh, P
Ralph, JW
Amato, A
Cannon, SC
Trivedi, J
Barohn, R
Crum, B
Mitsumoto, H
Pestronk, A
Meola, G
Conwit, R
Hanna, MG
Griggs, RC
AF Sansone, Valeria A.
Burge, James
McDermott, Michael P.
Smith, Patty C.
Herr, Barbara
Tawil, Rabi
Pandya, Shree
Kissel, John
Ciafaloni, Emma
Shieh, Perry
Ralph, Jeffrey W.
Amato, Antony
Cannon, Steve C.
Trivedi, Jaya
Barohn, Richard
Crum, Brian
Mitsumoto, Hiroshi
Pestronk, Alan
Meola, Giovanni
Conwit, Robin
Hanna, Michael G.
Griggs, Robert C.
CA Muscle Study Grp
TI Randomized, placebo-controlled trials of dichlorphenamide in periodic
paralysis
SO NEUROLOGY
LA English
DT Article
ID SKELETAL-MUSCLE CHANNELOPATHIES; SODIUM-CHANNEL MUTATIONS; HEALTH SURVEY
SF-36; ACETAZOLAMIDE TREATMENT; GENE-MUTATIONS; WEAKNESS; INACTIVATION;
PHENOTYPE; DYSTROPHY; DIAGNOSIS
AB Objective:To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis.Methods:Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase.Results:The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined).Conclusions:DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis.Classification of evidence:These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.
C1 [Sansone, Valeria A.] Univ Milan, NEMO Clin Ctr, I-20122 Milan, Italy.
[Meola, Giovanni] Univ Milan, IRCCS Policlin San Donato, I-20122 Milan, Italy.
[Burge, James; Hanna, Michael G.] UCL Inst Neurol, Ctr Neuromuscular Dis, MRC, Queen Sq, London, England.
[McDermott, Michael P.; Smith, Patty C.; Herr, Barbara; Tawil, Rabi; Pandya, Shree; Ciafaloni, Emma; Griggs, Robert C.] Univ Rochester, Rochester, NY 14627 USA.
[Kissel, John] Ohio State Univ, Columbus, OH 43210 USA.
[Shieh, Perry] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
[Ralph, Jeffrey W.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
[Amato, Antony] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Cannon, Steve C.; Trivedi, Jaya] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Barohn, Richard] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA.
[Crum, Brian] Mayo Clin, Rochester, MN USA.
[Mitsumoto, Hiroshi] Columbia Univ, New York, NY USA.
[Pestronk, Alan] Washington Univ, St Louis, MO USA.
[Conwit, Robin] NINDS, Off Clin Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Sansone, VA (reprint author), Univ Milan, NEMO Clin Ctr, I-20122 Milan, Italy.
EM valeria.sansone@unimi.it
OI meola, giovanni/0000-0001-6396-717X
FU NIH National Institute of Neurological Disorders and Stroke [R01
NS045686]; Muscular Dystrophy Association [93615]; NIH NCATS [UL1
TR000042, UL1 TR000040, UL1TR001070, UL1TR000001, UL1TR000124, UL1
TR000004, UL1 TR001105, UL1 TR000135]; NIH NCRR; NCATS [UL1 RR024160,
UL1 RR024131]; NIH NCRR [C06 RR20092, M01-02635, 1 UL1 RR025758]; NIH
NINDS [U10NS077384, R37-AR42703, RO1-AR063182]; MRC Centre Grant; UCL
Biomedical Research Centre Grant; NINDS; MDA
FX This study was supported by NIH National Institute of Neurological
Disorders and Stroke award R01 NS045686 (Robert C. Griggs, principal
investigator); the Muscular Dystrophy Association award 93615; NIH NCATS
awards UL1 TR000042, UL1 TR000040, UL1TR001070, UL1TR000001,
UL1TR000124, UL1 TR000004, UL1 TR001105, UL1 TR000135, and NIH NCRR;
NCATS awards UL1 RR024160 and UL1 RR024131; NIH NCRR awards C06 RR20092,
M01-02635, and 1 UL1 RR025758; NIH NINDS awards U10NS077384,
R37-AR42703, and RO1-AR063182 (S. Cannon, principal investigator); and
MRC Centre Grant and UCL Biomedical Research Centre Grant (M. Hanna,
principal investigator, Institute of Neurology, Queen Square, London).
NINDS and MDA funding was provided for participant travel support.
NR 36
TC 5
Z9 5
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD APR 12
PY 2016
VL 86
IS 15
BP 1408
EP 1416
DI 10.1212/WNL.0000000000002416
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DI9LW
UT WOS:000373825300001
PM 26865514
ER
PT J
AU Richter, B
Sliter, DA
Herhaus, L
Stolz, A
Wang, CX
Beli, P
Zaffagnini, G
Wild, P
Martens, S
Wagner, SA
Youle, RJ
Dikic, I
AF Richter, Benjamin
Sliter, Danielle A.
Herhaus, Lina
Stolz, Alexandra
Wang, Chunxin
Beli, Petra
Zaffagnini, Gabriele
Wild, Philipp
Martens, Sascha
Wagner, Sebastian A.
Youle, Richard J.
Dikic, Ivan
TI Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and
promotes selective autophagy of damaged mitochondria
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mitophagy; TBK1; OPTN; ubiquitin; phosphorylation
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKIN-MEDIATED MITOPHAGY;
PINK1-DEPENDENT PHOSPHORYLATION; ACTIVATE PARKIN; KINASE 1; UBIQUITIN;
OPTINEURIN; PINK1; MUTATIONS; DEGENERATION
AB Selective autophagy of damaged mitochondria requires autophagy receptors optineurin (OPTN), NDP52 (CALCOCO2), TAX1BP1, and p62 (SQSTM1) linking ubiquitinated cargo to autophagic membranes. By using quantitative proteomics, we show that Tank-binding kinase 1 (TBK1) phosphorylates all four receptors on several autophagy-relevant sites, including the ubiquitin-and LC3-binding domains of OPTN and p62/SQSTM1 as well as the SKICH domains of NDP52 and TAX1BP1. Constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to ubiquitin chains are essential for TBK1 recruitment and kinase activation on mitochondria. TBK1 in turn phosphorylates OPTN's UBAN domain at S473, thereby expanding the binding capacity of OPTN to diverse Ub chains. In combination with phosphorylation of S177 and S513, this posttranslational modification promotes recruitment and retention of OPTN/TBK1 on ubiquitinated, damaged mitochondria. Moreover, phosphorylation of OPTN on S473 enables binding to pS65 Ub chains and is also implicated in PINK1-driven and Parkin-independent mitophagy. Thus, TBK1-mediated phosphorylation of autophagy receptors creates a signal amplification loop operating in selective autophagy of damaged mitochondria.
C1 [Richter, Benjamin; Herhaus, Lina; Stolz, Alexandra; Wild, Philipp; Dikic, Ivan] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, D-60590 Frankfurt, Germany.
[Sliter, Danielle A.; Wang, Chunxin; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Beli, Petra] Inst Mol Biol, D-55128 Mainz, Germany.
[Zaffagnini, Gabriele; Martens, Sascha] Univ Vienna, Max F Perutz Labs, Vienna Bioctr, A-1030 Vienna, Austria.
[Wagner, Sebastian A.] Goethe Univ Frankfurt, Dept Med, Hematol Oncol, D-60590 Frankfurt, Germany.
[Dikic, Ivan] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, D-60438 Frankfurt, Germany.
[Dikic, Ivan] Univ Split, Sch Med, Inst Immunol, Split 21000, Croatia.
[Wild, Philipp] ETH, Inst Biochem, CH-8093 Zurich, Switzerland.
RP Dikic, I (reprint author), Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, D-60590 Frankfurt, Germany.; Dikic, I (reprint author), Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, D-60438 Frankfurt, Germany.; Dikic, I (reprint author), Univ Split, Sch Med, Inst Immunol, Split 21000, Croatia.
EM ivan.dikic@biochem2.de
RI Dikic, Ivan/O-4650-2015;
OI Dikic, Ivan/0000-0001-8156-9511; Beli, Petra/0000-0001-9507-9820;
Martens, Sascha/0000-0003-3786-8199
FU Deutsche Forschungsgemeinschaft [DI 931/3-1]; Cluster of Excellence
"Macromolecular Complexes" of the Goethe University Frankfurt [EXC115];
LOEWE Grant Ub-Net; LOEWE Centrum for Gene and Cell Therapy Frankfurt;
NIH-NINDS intramural program; European Molecular Biology Organization
(EMBO) long-term postdoctoral fellowship
FX We thank Simin Rahighi and Masato Akutsu for helpful discussions;
Evgenij Fiskin for the generation of HA-Parkin cells; Wade J. Harper and
Alban Ordureau for purified pS65 Ub chains; Patricia Boya for mitophagy
assays in mouse embryonic fibroblasts (MEFs); Giulio Superti-Furga for
complementary DNA constructs; Jochen H. Weishaupt and Stephen Taylor for
cells; and Dragan Maric and the National Institute of Neurological
Disorders and Stroke (NINDS) Flow Cytometry Core for FACS. This work was
supported by Deutsche Forschungsgemeinschaft Grant DI 931/3-1 (to I.D.);
the Cluster of Excellence "Macromolecular Complexes" of the Goethe
University Frankfurt (EXC115; to I.D.); LOEWE Grant Ub-Net (to I.D.) and
LOEWE Centrum for Gene and Cell Therapy Frankfurt (I.D. and B.R.); the
NIH-NINDS intramural program (R.J.Y., D.A.S., and C.W.); and an European
Molecular Biology Organization (EMBO) long-term postdoctoral fellowship
(to L.H.).
NR 43
TC 28
Z9 28
U1 10
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 12
PY 2016
VL 113
IS 15
BP 4039
EP 4044
DI 10.1073/pnas.1523926113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI8PG
UT WOS:000373762400047
PM 27035970
ER
PT J
AU Hall, AB
Papathanos, PA
Sharma, A
Cheng, CD
Akbari, OS
Assour, L
Bergman, NH
Cagnetti, A
Crisanti, A
Dottorini, T
Fiorentini, E
Galizi, R
Hnath, J
Jiang, XF
Koren, S
Nolan, T
Radune, D
Sharakhova, MV
Steele, A
Timoshevskiy, VA
Windbichler, N
Zhang, SM
Hahn, MW
Phillippy, AM
Emrich, SJ
Sharakhov, IV
Tu, ZJ
Besansky, NJ
AF Hall, Andrew Brantley
Papathanos, Philippos-Aris
Sharma, Atashi
Cheng, Changde
Akbari, Omar S.
Assour, Lauren
Bergman, Nicholas H.
Cagnetti, Alessia
Crisanti, Andrea
Dottorini, Tania
Fiorentini, Elisa
Galizi, Roberto
Hnath, Jonathan
Jiang, Xiaofang
Koren, Sergey
Nolan, Tony
Radune, Diane
Sharakhova, Maria V.
Steele, Aaron
Timoshevskiy, Vladimir A.
Windbichler, Nikolai
Zhang, Simo
Hahn, Matthew W.
Phillippy, Adam M.
Emrich, Scott J.
Sharakhov, Igor V.
Tu, Zhijian Jake
Besansky, Nora J.
TI Radical remodeling of the Y chromosome in a recent radiation of malaria
mosquitoes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Anopheles gambiae; PacBio; RNA-Seq; tandem repetitive DNA; Y-chromosome
ID ANOPHELES-GAMBIAE COMPLEX; DROSOPHILA-MELANOGASTER; SATELLITE DNA;
SEX-CHROMOSOMES; EVOLUTION; GENE; SEQUENCES; GENOME; HETEROCHROMATIN;
STEPHENSI
AB Y chromosomes control essential male functions in many species, including sex determination and fertility. However, because of obstacles posed by repeat-rich heterochromatin, knowledge of Y chromosome sequences is limited to a handful of model organisms, constraining our understanding of Y biology across the tree of life. Here, we leverage long single-molecule sequencing to determine the content and structure of the nonrecombining Y chromosome of the primary African malaria mosquito, Anopheles gambiae. We find that the An. gambiae Y consists almost entirely of a few massively amplified, tandemly arrayed repeats, some of which can recombine with similar repeats on the X chromosome. Sex-specific genome resequencing in a recent species radiation, the An. gambiae complex, revealed rapid sequence turnover within An. gambiae and among species. Exploiting 52 sex-specific An. gambiae RNA-Seq datasets representing all developmental stages, we identified a small repertoire of Y-linked genes that lack X gametologs and are not Y-linked in any other species except An. gambiae, with the notable exception of YG2, a candidate male-determining gene. YG2 is the only gene conserved and exclusive to the Y in all species examined, yet sequence similarity to YG2 is not detectable in the genome of a more distant mosquito relative, suggesting rapid evolution of Y chromosome genes in this highly dynamic genus of malaria vectors. The extensive characterization of the An. gambiae Y provides a long-awaited foundation for studying male mosquito biology, and will inform novel mosquito control strategies based on the manipulation of Y chromosomes.
C1 [Hall, Andrew Brantley; Jiang, Xiaofang; Sharakhov, Igor V.; Tu, Zhijian Jake] Virginia Polytech Inst & State Univ, Interdisciplinary PhD Program Genet Bioinformat &, Blacksburg, VA 24061 USA.
[Papathanos, Philippos-Aris; Cagnetti, Alessia; Crisanti, Andrea] Univ Perugia, Dept Expt Med, Sect Genom & Genet, I-06132 Perugia, Italy.
[Papathanos, Philippos-Aris; Crisanti, Andrea; Dottorini, Tania; Fiorentini, Elisa; Galizi, Roberto; Windbichler, Nikolai] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
[Sharma, Atashi; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Sharakhov, Igor V.] Virginia Polytech Inst & State Univ, Dept Entomol, Blacksburg, VA 24061 USA.
[Cheng, Changde; Emrich, Scott J.; Besansky, Nora J.] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Besansky, Nora J.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Akbari, Omar S.] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside Ctr Dis Vector Res, Dept Entomol, Riverside, CA 92521 USA.
[Assour, Lauren; Steele, Aaron; Emrich, Scott J.] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA.
[Bergman, Nicholas H.; Hnath, Jonathan; Radune, Diane] Natl Biodefense Anal & Countermeasures Ctr, Frederick, MD 21702 USA.
[Koren, Sergey; Phillippy, Adam M.] NHGRI, Genome Informat Sect, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Sharakhova, Maria V.; Sharakhov, Igor V.] Tomsk State Univ, Lab Evolutionary Cytogenet, Tomsk 634050, Russia.
[Zhang, Simo; Hahn, Matthew W.] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
[Hahn, Matthew W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Tu, Zhijian Jake] Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA.
[Cheng, Changde] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
RP Sharakhov, IV; Tu, ZJ (reprint author), Virginia Polytech Inst & State Univ, Interdisciplinary PhD Program Genet Bioinformat &, Blacksburg, VA 24061 USA.; Sharakhov, IV (reprint author), Virginia Polytech Inst & State Univ, Dept Entomol, Blacksburg, VA 24061 USA.; Besansky, NJ (reprint author), Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.; Besansky, NJ (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.; Sharakhov, IV (reprint author), Tomsk State Univ, Lab Evolutionary Cytogenet, Tomsk 634050, Russia.; Tu, ZJ (reprint author), Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA.
EM igor@vt.edu; jaketu@vt.edu; nbesansk@nd.edu
FU Eck Institute for Global Health, University of Notre Dame; European
Community [228421]; National Institutes of Health [R01AI076584,
R21AI112734, R21AI101459, R21AI094289, R21AI099528, R21AI105575,
HHSN272200900039C]; Foundation of the National Institutes of Health
through the VCTR program of the Grand Challenges in Global Health
Initiative; European Commission; Regione Umbria Grant I-MOVE; Rita-Levi
Montalcini Career Development Award; Marie Curie Intra-European
Fellowship for Career Development [PIEFGA-273268]; European Research
Council [335724]; National Science Foundation [DGE-1519168]; Department
of Education Graduate Assistance in Areas of National Need Fellowship;
Fralin Life Science Institute of Virginia Tech; National Human Genome
Research Institute, National Institutes of Health; Department of
Homeland Security (DHS) Science and Technology Directorate
[HSHQDC-07-C-00020]
FX We thank F. Catteruccia and S. N. Mitchell for sharing unpublished data;
J. Pease for assistance with simulations; M. Kern, M. Menichelli, M. K.
Lawniczak, I. Antoshechkin, T. Persampieri, R. Carballar, and R. D'Amato
for technical assistance and discussion; and two anonymous reviewers for
helpful suggestions. Genomic sequencing was funded in part by a grant
from the Eck Institute for Global Health, University of Notre Dame.
RNA-Seq was funded in part from a European Community Seventh Framework
Programme (FP7/2007-2013) under Grant 228421 (INFRAVEC). Individual
laboratories were funded as follows: National Institutes of Health
Grants R01AI076584 (to N.J.B. and M.W.H.), R21AI112734 (to N.J.B. and
S.J.E.), R21AI101459 (to N.J.B.), R21AI094289 and R21AI099528 (to
I.V.S.), R21AI105575 (to Z.J.T.), and HHSN272200900039C (to S.J.E.); the
Foundation of the National Institutes of Health through the VCTR program
of the Grand Challenges in Global Health Initiative (to N.J.B., A.
Crisanti, P.-A.P., and T. N.); European Commission and Regione Umbria
Grant I-MOVE (to R.G., E.F., and P.-A.P.); Rita-Levi Montalcini Career
Development Award (to P.-A.P.); Marie Curie Intra-European Fellowship
for Career Development PIEFGA-273268 (to T.D.); European Research
Council Grant 335724 (to N.W.); National Science Foundation Graduate
Research Fellowship Grant DGE-1519168 (to A.B.H.); Department of
Education Graduate Assistance in Areas of National Need Fellowship (to
A. Steele); and Fralin Life Science Institute of Virginia Tech (to
I.V.S. and Z.J.T.). This research was supported in part by the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health (to S. K. and A.M.P.). The
contributions of N.H.B., J.H., and D.R. were funded under Agreement
HSHQDC-07-C-00020 awarded by the Department of Homeland Security (DHS)
Science and Technology Directorate for the management and operation of
the National Biodefense Analysis and Countermeasures Center (NBACC), a
Federally Funded Research and Development Center. The views and
conclusions contained in this document are those of the authors and
should not be interpreted as necessarily representing the official
policies, either expressed or implied, of the US Department of Homeland
Security. In no event shall the DHS, NBACC, or Battelle National
Biodefense Institute (BNBI) have any responsibility or liability for any
use, misuse, inability to use, or reliance upon the information
contained herein. The Department of Homeland Security does not endorse
any products or commercial services mentioned in this publication.
NR 74
TC 7
Z9 7
U1 15
U2 23
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 12
PY 2016
VL 113
IS 15
BP E2114
EP E2123
DI 10.1073/pnas.1525164113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI8PG
UT WOS:000373762400006
PM 27035980
ER
PT J
AU Tincati, C
Douek, DC
Marchetti, G
AF Tincati, Camilla
Douek, Daniel C.
Marchetti, Giulia
TI Gut barrier structure, mucosal immunity and intestinal microbiota in the
pathogenesis and treatment of HIV infection
SO AIDS RESEARCH AND THERAPY
LA English
DT Review
DE Microbial translocation; Gastrointestinal barrier; Mucosal immunity;
Microbiota
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL
THERAPY; TRYPTOPHAN CATABOLISM; SYSTEMIC INFLAMMATION; EPITHELIAL
BARRIER; PREDICT MORTALITY; VIRAL REPLICATION; TYPE-1 INFECTION;
PLASMA-LEVELS
AB Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.
C1 [Tincati, Camilla; Marchetti, Giulia] Univ Milan, San Paolo Hosp, Dept Hlth Sci, Clin Infect Dis, Via Rudini 8, I-20142 Milan, Italy.
[Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Marchetti, G (reprint author), Univ Milan, San Paolo Hosp, Dept Hlth Sci, Clin Infect Dis, Via Rudini 8, I-20142 Milan, Italy.
EM giulia.marchetti@unimi.it
FU Italian Ministry of Health (Regione Lombardia, "Giovani Ricercatori")
[GR-2009-1592029]
FX GM received a grant from the Italian Ministry of Health (Regione
Lombardia, "Giovani Ricercatori" #GR-2009-1592029).
NR 76
TC 6
Z9 6
U1 10
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-6405
J9 AIDS RES THER
JI Aids Res. Ther.
PD APR 11
PY 2016
VL 13
AR 19
DI 10.1186/s12981-016-0103-1
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA DK3KR
UT WOS:000374816000001
PM 27906073
ER
PT J
AU Gerlits, O
Wymore, T
Das, A
Shen, CH
Parks, JM
Smith, JC
Weiss, KL
Keen, DA
Blakeley, MP
Louis, JM
Langan, P
Weber, IT
Kovalevsky, A
AF Gerlits, Oksana
Wymore, Troy
Das, Amit
Shen, Chen-Hsiang
Parks, Jerry M.
Smith, Jeremy C.
Weiss, Kevin L.
Keen, David A.
Blakeley, Matthew P.
Louis, John M.
Langan, Paul
Weber, Irene T.
Kovalevsky, Andrey
TI Long-Range Electrostatics-Induced Two-Proton Transfer Captured by
Neutron Crystallography in an Enzyme Catalytic Site
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE aspartic protease; enzymes; neutron crystallography; proton transfer;
QM; MM modeling
ID X-RAY CRYSTALLOGRAPHY; BARRIER HYDROGEN-BOND; PROTON-TRANSFER; HIV-1
PROTEASE; FLUORESCENT PROTEIN; ATOMIC-RESOLUTION; CRYSTAL-STRUCTURES;
BINDING-SITES; INHIBITOR; MECHANISM
AB Neutron crystallography was used to directly locate two protons before and after a pH-induced two-proton transfer between catalytic aspartic acid residues and the hydroxy group of the bound clinical drug darunavir, located in the catalytic site of enzyme HIV-1 protease. The two-proton transfer is triggered by electrostatic effects arising from protonation state changes of surface residues far from the active site. The mechanism and pH effect are supported by quantum mechanics/molecular mechanics (QM/MM) calculations. The low-pH proton configuration in the catalytic site is deemed critical for the catalytic action of this enzyme and may apply more generally to other aspartic proteases. Neutrons therefore represent a superb probe to obtain structural details for proton transfer reactions in biological systems at a truly atomic level.
C1 [Gerlits, Oksana; Weiss, Kevin L.; Langan, Paul; Kovalevsky, Andrey] Oak Ridge Natl Lab, Biol & Soft Matter Div, Oak Ridge, TN 37831 USA.
[Wymore, Troy; Parks, Jerry M.; Smith, Jeremy C.] Oak Ridge Natl Lab, UT ORNL Ctr Mol Biophys, Biosci Div, Oak Ridge, TN 37831 USA.
[Das, Amit] BARC Trombay, Div Solid State Phys, Mumbai 400085, Maharashtra, India.
[Shen, Chen-Hsiang; Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30302 USA.
[Shen, Chen-Hsiang; Weber, Irene T.] Georgia State Univ, Dept Biol, POB 4010, Atlanta, GA 30302 USA.
[Keen, David A.] Rutherford Appleton Lab, ISIS Facil, Didcot OX11 0QX, Oxon, England.
[Blakeley, Matthew P.] Inst Laue Langevin, Large Scale Structures Grp, 71 Ave Martyrs CS 20156, F-38042 Grenoble 9, France.
[Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Kovalevsky, A (reprint author), Oak Ridge Natl Lab, Biol & Soft Matter Div, Oak Ridge, TN 37831 USA.
EM kovalevskyay@ornl.gov
RI Weiss, Kevin/I-4669-2013; Blakeley, Matthew/G-7984-2015; Langan,
Paul/N-5237-2015;
OI Weiss, Kevin/0000-0002-6486-8007; Blakeley, Matthew/0000-0002-6412-4358;
Langan, Paul/0000-0002-0247-3122; Kovalevsky, Andrey/0000-0003-4459-9142
FU DOE Office of Biological and Environmental Research (BER); DOE Office of
Basic Energy Sciences (BES); CSMB; NIH [R01GM02920]
FX We thank the Center for Structural Molecular Biology (CSMB) at BES
Scientific User Facilities Division, supported by the DOE Office of
Biological and Environmental Research (BER), for facility use. O. G., P.
L., and A. K. were partly supported by the DOE Office of Basic Energy
Sciences (BES). K. L. W. was partly supported by CSMB. I. T. W. was
partly supported by an NIH grant R01GM02920. The authors thank Institut
Laue Langevin (beamline LADI-III) and Oak Ridge National Laboratory
(IMAGINE beamline) for neutron beam time.
NR 41
TC 5
Z9 5
U1 10
U2 32
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD APR 11
PY 2016
VL 55
IS 16
BP 4924
EP 4927
DI 10.1002/anie.201509989
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DJ8XB
UT WOS:000374496100007
PM 26958828
ER
PT J
AU Zhang, T
Ye, YH
AF Zhang, Ting
Ye, Yihong
TI Doa1 is a MAD adaptor for Cdc48
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID UBIQUITIN-BINDING DOMAIN; PROTEIN-DEGRADATION; QUALITY-CONTROL;
AAA-ATPASE; P97; PROTEASOME; COFACTORS; INTERACTS; MEDIATE; SYSTEM
C1 [Zhang, Ting; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
NR 20
TC 0
Z9 0
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD APR 11
PY 2016
VL 213
IS 1
BP 7
EP 9
DI 10.1083/jcb.201603078
PG 3
WC Cell Biology
SC Cell Biology
GA DJ4WL
UT WOS:000374208700004
PM 27044894
ER
PT J
AU Yang, YB
Kelly, P
Shaffer, AL
Schmitz, R
Yoo, HM
Liu, XY
Huang, DW
Webster, D
Young, RM
Nakagawa, M
Ceribelli, M
Wright, GW
Yang, YD
Zhao, H
Yu, X
Xu, WH
Chan, WC
Jaffe, ES
Gascoyne, RD
Campo, E
Rosenwald, A
Ott, G
Delabie, J
Rimsza, L
Staudt, LM
AF Yang, Yibin
Kelly, Priscilla
Shaffer, Arthur L.
Schmitz, Roland
Yoo, Hee Min
Liu, Xinyue
Huang, Da Wei
Webster, Daniel
Young, Ryan M.
Nakagawa, Masao
Ceribelli, Michele
Wright, George W.
Yang, Yandan
Zhao, Hong
Yu, Xin
Xu, Weihong
Chan, Wing C.
Jaffe, Elaine S.
Gascoyne, Randy D.
Campo, Elias
Rosenwald, Andreas
Ott, German
Delabie, Jan
Rimsza, Lisa
Staudt, Louis M.
TI Targeting Non-proteolytic Protein Ubiquitination for the Treatment of
Diffuse Large B Cell Lymphoma
SO CANCER CELL
LA English
DT Article
ID NF-KAPPA-B; CHAIN ASSEMBLY COMPLEX; ALPHA-DEPENDENT APOPTOSIS; SIGNALING
COMPLEX; ANTAGONISTS INDUCE; SOMATIC MUTATIONS; MULTIPLE-MYELOMA; CARD11
MUTATIONS; CODING GENOME; IKK COMPLEX
AB Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate I kappa B kinase (IKK) and the classical NF-kappa B pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-kappa B activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetics target cIAP1/2 for destruction, and consequently suppress NF-kB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL.
C1 [Kelly, Priscilla; Shaffer, Arthur L.; Schmitz, Roland; Yoo, Hee Min; Liu, Xinyue; Huang, Da Wei; Webster, Daniel; Young, Ryan M.; Nakagawa, Masao; Ceribelli, Michele; Yang, Yandan; Zhao, Hong; Yu, Xin; Xu, Weihong; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA.
[Wright, George W.] NCI, Biometr Res Branch, Div Canc Diag & Treatment, NIH, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA.
[Chan, Wing C.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Jaffe, Elaine S.] NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
[Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dr Margarete Fischer Bosch Inst Clin Pharmacol, Dept Clin Pathol, D-70376 Stuttgart, Germany.
[Delabie, Jan] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
[Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
RI Campo, elias/O-7192-2016
OI Campo, elias/0000-0001-9850-9793
FU Lymphoma/Leukemia Molecular Profiling Project (LLMPP); Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research; Dr. Mildred Scheel Stiftung fur Krebsforschung
(Deutsche Krebshilfe)
FX The authors thank the patients for their participation. We wish to thank
Kathleen Meyer for her assistance with GEO submissions, and the members
of the Coriell Genotyping and Microarray Center for their assistance
with Affymetrix SNP6.0 array. This study was conducted under the
auspices of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP).
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. R.S. was
supported by the Dr. Mildred Scheel Stiftung fur Krebsforschung
(Deutsche Krebshilfe). D.W. is the Philip O'Bryan Montgomery, Jr., MD,
Fellow of the Damon Runyon Cancer Research Foundation (DRG-2208-14).
NR 72
TC 13
Z9 13
U1 5
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD APR 11
PY 2016
VL 29
IS 4
BP 494
EP 507
DI 10.1016/j.ccell.2016.03.006
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DI9WY
UT WOS:000373854600013
PM 27070702
ER
PT J
AU Ricketts, CJ
Crooks, DR
Sourbier, C
Schmidt, LS
Srinivasan, R
Linehan, WM
AF Ricketts, Christopher J.
Crooks, Daniel R.
Sourbier, Carole
Schmidt, Laura S.
Srinivasan, Ramaprasad
Linehan, W. Marston
TI SnapShot: Renal Cell Carcinoma
SO CANCER CELL
LA English
DT Editorial Material
ID CANCER; MUTATIONS; GERMLINE; FUMARATE
C1 [Ricketts, Christopher J.; Crooks, Daniel R.; Sourbier, Carole; Schmidt, Laura S.; Srinivasan, Ramaprasad; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Ricketts, CJ (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 10
TC 1
Z9 1
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD APR 11
PY 2016
VL 29
IS 4
BP 610
EP +
DI 10.1016/j.ccell.2016.03.021
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DI9WY
UT WOS:000373854600024
PM 27070709
ER
PT J
AU Zimmer, ER
Torrez, VR
Kalinine, E
Augustin, MC
Zenki, KC
Almeida, RF
Hansel, G
Muller, AP
Souza, DO
Machado-Vieira, R
Portela, LV
AF Zimmer, Eduardo R.
Torrez, Vitor R.
Kalinine, Eduardo
Augustin, Marina C.
Zenki, Kamila C.
Almeida, Roberto F.
Hansel, Gisele
Muller, Alexandre P.
Souza, Diogo O.
Machado-Vieira, Rodrigo
Portela, Luis V.
TI Long-term NMDAR antagonism correlates reduced astrocytic glutamate
uptake with anxiety-like phenotype (vol 9, 219, 2015)
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Correction
DE anxiety; astrocytes; behavior; glutamate; memantine
C1 [Zimmer, Eduardo R.; Torrez, Vitor R.; Kalinine, Eduardo; Augustin, Marina C.; Zenki, Kamila C.; Almeida, Roberto F.; Hansel, Gisele; Muller, Alexandre P.; Souza, Diogo O.; Portela, Luis V.] Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil.
[Kalinine, Eduardo] Univ Fed Sergipe, Dept Physiol, Sao Cristovao, Brazil.
[Muller, Alexandre P.] Univ Extremo Sul Catarinense, Lab Exercise Biochem & Physiol, Criciuma, Brazil.
[Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci, LIM 27, Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
RP Portela, LV (reprint author), Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil.
EM roskaportela@gmail.com
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Zimmer, Eduardo/I-2932-2015
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Zimmer,
Eduardo/0000-0002-5349-0053
NR 1
TC 0
Z9 0
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD APR 11
PY 2016
VL 10
AR 93
DI 10.3389/fncel.2016.00093
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA DI8IU
UT WOS:000373745500001
PM 27147966
ER
PT J
AU Naydenov, NG
Feygin, A
Wang, DD
Kuemmerle, JF
Harris, G
Conti, MA
Adelstein, RS
Ivanov, AI
AF Naydenov, Nayden G.
Feygin, Alex
Wang, Dongdong
Kuemmerle, John F.
Harris, Gianni
Conti, Mary Anne
Adelstein, Robert S.
Ivanov, Andrei I.
TI Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and
Plays a Protective Role During Experimental Colitis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID APICAL JUNCTIONAL COMPLEX; INFLAMMATORY-BOWEL-DISEASE; TIGHT JUNCTION;
LIGHT-CHAIN; CELL-ADHESION; PERMEABILITY; ACTIVATION; EXPRESSION;
MEMBRANE; PROTEIN
AB The actin cytoskeleton is a critical regulator of intestinal mucosal barrier permeability, and the integrity of epithelial adherens junctions (AJ) and tight junctions (TJ). Non muscle myosin II (NM II) is a key cytoskeletal motor that controls actin filament architecture and dynamics. While NM II has been implicated in the regulation of epithelial junctions in vitro, little is known about its roles in the intestinal mucosa in vivo. In this study, we generated a mouse model with an intestinal epithelial-specific knockout of NM IIA heavy chain (NM IIA cKO) and examined the structure and function of normal gut barrier, and the development of experimental colitis in these animals. Unchallenged NM IIA cKO mice showed increased intestinal permeability and altered expression/localization of several AJ/TJ proteins. They did not develop spontaneous colitis, but demonstrated signs of a low-scale mucosal inflammation manifested by prolapses, lymphoid aggregates, increased cytokine expression, and neutrophil infiltration in the gut. NM IIA cKO animals were characterized by a more severe disruption of the gut barrier and exaggerated mucosal injury during experimentally-induced colitis. Our study provides the first evidence that NM IIA plays important roles in establishing normal intestinal barrier, and protection from mucosal inflammation in vivo.
C1 [Naydenov, Nayden G.; Feygin, Alex; Wang, Dongdong; Ivanov, Andrei I.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Kuemmerle, John F.] Virginia Commonwealth Univ, Dept Internal Med, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Harris, Gianni] Univ Rochester, Sch Med, Dept Med, Rochester, NY USA.
[Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Ivanov, Andrei I.] Virginia Commonwealth Univ, VCU Massey Canc Ctr, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Ivanov, Andrei I.] Virginia Inst Mol Med, Richmond, VA 23298 USA.
RP Ivanov, AI (reprint author), Virginia Commonwealth Univ, Dept Human & Mol Genet, Med Coll Virginia Campus, Richmond, VA 23298 USA.; Ivanov, AI (reprint author), Virginia Commonwealth Univ, VCU Massey Canc Ctr, Med Coll Virginia Campus, Richmond, VA 23298 USA.; Ivanov, AI (reprint author), Virginia Inst Mol Med, Richmond, VA 23298 USA.
EM Andrei.Ivanov@vcuhealth.org
OI Adelstein, Robert/0000-0002-8683-2144
FU VCU Massey Cancer Center; NIH-NCI [P30CA016059]; NIH-NINDS Center
[5P30NS047463]; National Institute of Health [RO1 DK083968, R01
DK084953]; Crohn's and Colitis Foundation of America [254881]
FX Services in support of this study were provided by the VCU Massey Cancer
Center, supported in part with funding from NIH-NCI core grant
P30CA016059. Microscopy was performed at the VCU Department of Anatomy
and Neurobiology Microscopy Facility, supported, in part, with funding
from the NIH-NINDS Center core grant 5P30NS047463. This work was
supported by National Institute of Health grants RO1 DK083968, R01
DK084953 to A.I.I. and by the Crohn's and Colitis Foundation of America
research fellowship award 254881 to N.G.N.
NR 53
TC 6
Z9 6
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 11
PY 2016
VL 6
AR 24161
DI 10.1038/srep24161
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI8PP
UT WOS:000373763400001
PM 27063635
ER
PT J
AU Wang, CS
Wee, Y
Yang, CH
Melvin, JE
Baker, OJ
AF Wang, Ching-Shuen
Wee, Yinshen
Yang, Chieh-Hsiang
Melvin, James E.
Baker, Olga J.
TI ALX/FPR2 Modulates Anti-Inflammatory Responses in Mouse Submandibular
Gland
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RESOLVING LIPID MEDIATORS; SALIVARY-GLAND; ACUTE-INFLAMMATION;
SJOGRENS-SYNDROME; MICROGLIAL ACTIVATION; ACINAR-CELLS; HOST-DEFENSE;
RECEPTOR; RESOLUTION; EXPRESSION
AB Activation of the G-protein coupled formyl peptide receptor 2 (ALX/FPR2) by the lipid mediators lipoxin A(4) and resolvin D1 (RvD1) promotes resolution of inflammation. Our previous in vitro studies indicate that RvD1 activation of ALX/FPR2 resolves cytokine-mediated inflammatory responses in mammalian cells. However, the impact of ALX/FPR2 activation on salivary gland function in vivo is unknown. The objective of this study was to determine whether submandibular glands (SMG) from ALX/FPR2(-/-) mice display enhanced inflammatory responses to lipopolysaccharides (LPS) stimulation. For these studies, C57BL/6 and ALX/FPR2(-/-) mice at age 8-12-week-old were treated with LPS by i.p for 24 h. Salivary gland structure and function were analyzed by histopathological assessment, saliva flow rate, quantitative PCR, Western blot analyses and immunofluorescence. Our results showed the following events in the ALX/FPR2(-/-) mice treated with LPS: a) upregulated inflammatory cytokines and decreased M3R (Muscarinic Acetylcholine receptor M3) and AQP5 (Aquaporin 5) protein expression, b) decreased saliva secretion, c) increased apoptosis, d) alteration of tight junction and neuronal damage. Overall, our data suggest that the loss of ALX/FPR2 results in unresolved acute inflammation and SMG dysfunction (xerostomia) in response to LPS that is similar to human salivary gland dysfunction induced by bacterial infection.
C1 [Wang, Ching-Shuen; Baker, Olga J.] Univ Utah, Sch Dent, Salt Lake City, UT 84108 USA.
[Wee, Yinshen] Univ Utah, Sch Med, Dept Pathol, Div Microbiol & Immunol, Salt Lake City, UT 84102 USA.
[Yang, Chieh-Hsiang] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
[Melvin, James E.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Baker, OJ (reprint author), Univ Utah, Sch Dent, Salt Lake City, UT 84108 USA.
EM olga.baker@hsc.utah.edu
FU National Institutes of Health-National Institute of Dental and
Craniofacial Research Grants [R01DE022971, R01DE021697, R01DE021697S1,
R01DE021697S2]; Intramural Research Program of the NIH, NIDCR
FX We thank Dr. Mauro Perretti (William Harvey Research Institute, Barts
and The London School of Medicine, United Kingdom) for sharing
ALX/FPR2-/- mice for our study. This study is supported by
the National Institutes of Health-National Institute of Dental and
Craniofacial Research Grants R01DE022971, R01DE021697, R01DE021697S1 and
R01DE021697S2 (to OB) and in part by the Intramural Research Program of
the NIH, NIDCR (to JEM).
NR 60
TC 2
Z9 2
U1 6
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 11
PY 2016
VL 6
AR 24244
DI 10.1038/srep24244
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI8QG
UT WOS:000373765300001
PM 27064029
ER
PT J
AU Doyle, AD
Yamada, KM
AF Doyle, Andrew D.
Yamada, Kenneth M.
TI Mechanosensing via cell-matrix adhesions in 3D microenvironments
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Review
DE Adhesion; Mechanotransduction; Collagen; 3D migration; Contractility;
Dynamics
ID 3-DIMENSIONAL COLLAGEN MATRICES; FOCAL ADHESIONS; EXTRACELLULAR-MATRIX;
MYOSIN-IIA; MIGRATION; INTEGRIN; DYNAMICS; VINCULIN; FORCE; FIBROBLASTS
AB The extracellular matrix (ECM) microenvironment plays a central role in cell migration by providing physiochemical information that influences overall cell behavior. Much of this external information is accessed by direct interaction of the cell with ECM ligands and structures via integrin-based adhesions that are hypothesized to act as mechanosensors for testing the surrounding microenvironment. Our current understanding of these mechanical complexes is derived primarily from studies of cellular adhesions formed on two-dimensional (2D) substrates in vitro. Yet the rules of cell/ECM engagement and mechanosensing in three-dimensional (3D) microenvironments are invariably more complex under both in vitro and in vivo conditions. Here we review the current understanding of how cellular mechanosensing occurs through adhesion complexes within 3D microenvironments and discuss how these mechanisms can vary and differ from interactions on 2D substrates. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Doyle, Andrew D.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Doyle, AD; Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
EM adoyle@mail.nih.gov; kyamada@dir.nidcr.nih.gov
FU NIDCR Division of Intramural Research [ZIA DE000524, ZIA DE000718]
FX We would like to thank Brian DuChez, Will Daley, Josh Collins, and Dan
Sykora for critical reading of this review. This work was supported by
the NIDCR Division of Intramural Research (ZIA DE000524 and ZIA
DE000718).
NR 80
TC 7
Z9 7
U1 15
U2 29
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD APR 10
PY 2016
VL 343
IS 1
SI SI
BP 60
EP 66
DI 10.1016/j.yexcr.2015.10.033
PG 7
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL2WF
UT WOS:000375495200010
PM 26524505
ER
PT J
AU Li, L
Chen, JG
Chen, X
Tang, J
Guo, H
Wang, XF
Qian, J
Luo, GJ
He, FP
Lu, XM
Ding, YB
Yang, YC
Huang, WT
Hou, GJ
Lin, XM
Ouyang, Q
Li, HY
Wang, RY
Jiang, F
Pu, R
Lu, JH
Jin, M
Tan, YX
Gonzalez, FJ
Cao, GW
Wu, MC
Wen, H
Wu, TC
Jin, L
Chen, L
Wang, HY
AF Li, Liang
Chen, Jianguo
Chen, Xin
Tang, Jing
Guo, Huan
Wang, Xiaofeng
Qian, Ji
Luo, Guijuan
He, Fangping
Lu, Xiaomei
Ding, Yibo
Yang, Yingchen
Huang, Wentao
Hou, Guojun
Lin, Ximeng
Ouyang, Qin
Li, Hengyu
Wang, Ruoyu
Jiang, Feng
Pu, Rui
Lu, Jianhua
Jin, Mudan
Tan, Yexiong
Gonzalez, Frank J.
Cao, Guangwen
Wu, Mengchao
Wen, Hao
Wu, Tangchun
Jin, Li
Chen, Lei
Wang, Hongyang
TI Serum miRNAs as predictive and preventive biomarker for pre-clinical
hepatocellular carcinoma
SO CANCER LETTERS
LA English
DT Article
DE Hepatocellular carcinoma; Circulating miRNAs; Biomarker; Prediction;
Prevention
ID ALPHA-FETOPROTEIN; CHRONIC HEPATITIS; CANCER; MICRORNAS; MANAGEMENT;
DIAGNOSIS; DESIGN
AB The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6-12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using alpha-fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Li, Liang; Chen, Xin; Tang, Jing; Luo, Guijuan; Yang, Yingchen; Huang, Wentao; Hou, Guojun; Lin, Ximeng; Ouyang, Qin; Li, Hengyu; Jin, Mudan; Tan, Yexiong; Chen, Lei; Wang, Hongyang] Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China.
[Li, Liang; Chen, Xin; Tang, Jing; Luo, Guijuan; Tan, Yexiong; Chen, Lei; Wang, Hongyang] Natl Ctr Liver Canc, Shanghai, Peoples R China.
[Chen, Jianguo; Lu, Jianhua] Qidong Liver Canc Inst, Qidong 226200, Jiangsu, Peoples R China.
[Chen, Jianguo; Lu, Jianhua] Nantong Univ, Liver Canc Inst, Qidong 226200, Jiangsu, Peoples R China.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, MOE Key Lab Environm & Hlth, 13 Hangkong Rd, Wuhan 430030, Peoples R China.
[Wang, Xiaofeng; Qian, Ji; Jin, Li] Fudan Univ, TaiZhou Inst Hlth Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Wang, Xiaofeng; Qian, Ji; Jin, Li] Fudan Univ, TaiZhou Inst Hlth Sci, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
[Wang, Xiaofeng; Qian, Ji; Jin, Li] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, Shanghai 200433, Peoples R China.
[He, Fangping; Lu, Xiaomei; Wen, Hao] Xinjiang Med Univ, Affiliated Hosp 1, State Key Lab Breeding Base Xinjiang Major Dis Re, Xinjiang 830054, Peoples R China.
[Ding, Yibo; Pu, Rui; Cao, Guangwen] Second Mil Med Univ, Dept Epidemiol, Shanghai 200433, Peoples R China.
[Wang, Ruoyu; Wu, Mengchao] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China.
[Jiang, Feng] Canc Hosp Jiangsu Prov, Jiangsu Key Lab Mol & Translat Canc Res, Nanjing, Jiangsu, Peoples R China.
[Gonzalez, Frank J.; Chen, Lei] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Hongyang] Shanghai Jiao Tong Univ, RenJi Hosp, Inst Canc, Natl Lab Oncogenes & Related Genes, Shanghai 200441, Peoples R China.
RP Chen, L; Wang, HY (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China.; Chen, L; Wang, HY (reprint author), Natl Ctr Liver Canc, Shanghai, Peoples R China.; Chen, L (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Wang, HY (reprint author), Shanghai Jiao Tong Univ, RenJi Hosp, Inst Canc, Natl Lab Oncogenes & Related Genes, Shanghai 200441, Peoples R China.
EM Chenlei@smmu.edu.cn; hywangk@vip.sina.com
RI Jin, Li/C-1468-2009
OI Jin, Li/0000-0002-4546-2415
FU State Key Project for Liver Cancer [2012ZX10002-009]; National Research
Program of China [2012CB316503, 2012AA02A201]; National Natural Science
Foundation of China [81221061, 81422032, 81272212, 81300306, 81372674];
Natural Science Foundation of Shanghai [134119a3700, 20154Y0054]
FX We gratefully acknowledge the support from the State Key Project for
Liver Cancer (2012ZX10002-009), the National Research Program of China
(2012CB316503, 2012AA02A201), National Natural Science Foundation of
China (81221061, 81422032, 81272212, 81300306 and 81372674) and Natural
Science Foundation of Shanghai (134119a3700, 20154Y0054).
NR 22
TC 2
Z9 3
U1 6
U2 22
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD APR 10
PY 2016
VL 373
IS 2
BP 234
EP 240
DI 10.1016/j.canlet.2016.01.028
PG 7
WC Oncology
SC Oncology
GA DG1OR
UT WOS:000371837900011
PM 26850373
ER
PT J
AU Jacobs, M
Benovoy, M
Chang, LC
Arai, AE
Hsu, LY
AF Jacobs, Matthew
Benovoy, Mitchel
Chang, Lin-Ching
Arai, Andrew E.
Hsu, Li-Yueh
TI Evaluation of an automated method for arterial input function detection
for first-pass myocardial perfusion cardiovascular magnetic resonance
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Cardiovascular magnetic resonance; Myocardial perfusion imaging;
Arterial input function
ID CONTRAST-ENHANCED MRI; QUANTITATIVE CORONARY-ANGIOGRAPHY;
POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; QUANTIFICATION; VALIDATION;
DISEASE; ACCURACY; IMAGES; CMR
AB Background: Quantitative assessment of myocardial blood flow (MBF) with first-pass perfusion cardiovascular magnetic resonance (CMR) requires a measurement of the arterial input function (AIF). This study presents an automated method to improve the objectivity and reduce processing time for measuring the AIF from first-pass perfusion CMR images. This automated method is used to compare the impact of different AIF measurements on MBF quantification.
Methods: Gadolinium-enhanced perfusion CMR was performed on a 1.5 T scanner using a saturation recovery dual-sequence technique. Rest and stress perfusion series from 270 clinical studies were analyzed. Automated image processing steps included motion correction, intensity correction, detection of the left ventricle (LV), independent component analysis, and LV pixel thresholding to calculate the AIF signal. The results were compared with manual reference measurements using several quality metrics based on the contrast enhancement and timing characteristics of the AIF. The median and 95 % confidence interval (CI) of the median were reported. Finally, MBF was calculated and compared in a subset of 21 clinical studies using the automated and manual AIF measurements.
Results: Two clinical studies were excluded from the comparison due to a congenital heart defect present in one and a contrast administration issue in the other. The proposed method successfully processed 99.63 % of the remaining image series. Manual and automatic AIF time-signal intensity curves were strongly correlated with median correlation coefficient of 0.999 (95 % CI [0.999, 0.999]). The automated method effectively selected bright LV pixels, excluded papillary muscles, and required less processing time than the manual approach. There was no significant difference in MBF estimates between manually and automatically measured AIFs (p = NS). However, different sizes of regions of interest selection in the LV cavity could change the AIF measurement and affect MBF calculation (p = NS to p = 0.03).
Conclusion: The proposed automatic method produced AIFs similar to the reference manual method but required less processing time and was more objective. The automated algorithm may improve AIF measurement from the first-pass perfusion CMR images and make quantitative myocardial perfusion analysis more robust and readily available.
C1 [Jacobs, Matthew; Benovoy, Mitchel; Arai, Andrew E.; Hsu, Li-Yueh] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Jacobs, Matthew; Chang, Lin-Ching] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
[Benovoy, Mitchel] Ecole Polytech, Dept Biomed Engn, Montreal, PQ H3C 3A7, Canada.
RP Hsu, LY (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lyhsu@mail.nih.gov
FU National Heart, Lung and Blood Institute [ZIA HL006137-05]
FX This project was funded and supported by the intramural research program
of the National Heart, Lung and Blood Institute (ZIA HL006137-05).
NR 33
TC 0
Z9 0
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD APR 8
PY 2016
VL 18
AR 17
DI 10.1186/s12968-016-0239-0
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DK4CP
UT WOS:000374864800001
PM 27055445
ER
PT J
AU Wang, J
Zhao, SD
Shugart, YY
Zhou, ZH
Jin, CH
Yuan, JM
Wang, GQ
Wang, D
Cheng, ZH
Zhang, FQ
AF Wang, Jun
Zhao, Shuidi
Shugart, Yin Yao
Zhou, Zhenhe
Jin, Chunhui
Yuan, Jianmin
Wang, Guoqiang
Wang, Dong
Cheng, Zaohuo
Zhang, Fuquan
TI No association between ZNF804A rs1344706 and schizophrenia in a
case-control study of Han Chinese
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Schizophrenia; Zinc finger protein 804A; rs1344706; Han Chinese
ID BIPOLAR DISORDER; GENE; POLYMORPHISM; VARIANTS; SUSCEPTIBILITY;
POPULATION; PSYCHOSIS; PROTEIN; RISK
AB Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 within the gene ZNF804A was a promising risk variant for schizophrenia in European populations. However, existing results are inconsistent in Han Chinese. Hoping to validate the association of rs1344706 with schizophrenia susceptibility in Han Chinese, we conducted a case-control study in 1284 cases and 990 healthy controls from Jiangsu Province, China. We did not detect any significant between-group difference (all P > 0.05) in either allele or genotype frequency under any genetic model between cases and controls. Stratified analysis by sex also failed to find any significant association. Our results did not support the association of rs1344706 with schizophrenia in Han Chinese, and further association studies with large samples from other ethnic backgrounds and focus on more SNPs of ZNF804A are warranted. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Wang, Jun; Zhou, Zhenhe; Jin, Chunhui; Yuan, Jianmin; Wang, Guoqiang; Wang, Dong; Cheng, Zaohuo; Zhang, Fuquan] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi 214151, Jiangsu, Peoples R China.
[Zhao, Shuidi] Nanjing Med Univ, Affiliated Hosp 2, Nanjing 210011, Jiangsu, Peoples R China.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Cheng, ZH; Zhang, FQ (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi 214151, Jiangsu, Peoples R China.
EM chengzaohuo@126.com; zhangfq@njmu.edu.cn
FU National Natural Science Foundation of China [81471364]; Joint project
of Management Center of Wuxi Hospital [YGZXL1307]
FX We thank all participants in the study. This work was supported by the
National Natural Science Foundation of China (Grant number: 81471364),
and the Joint project of Management Center of Wuxi Hospital (Grant
number: YGZXL1307).
NR 33
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Z9 1
U1 1
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD APR 8
PY 2016
VL 618
BP 14
EP 18
DI 10.1016/j.neulet.2016.02.048
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA DK0NS
UT WOS:000374610100003
PM 26934312
ER
PT J
AU Hu, JX
Stern, M
Gimenez, LE
Wanka, L
Zhu, L
Rossi, M
Meister, J
Inoue, A
Beck-Sickinger, AG
Gurevich, VV
Wess, J
AF Hu, Jianxin
Stern, Matthew
Gimenez, Luis E.
Wanka, Lizzy
Zhu, Lu
Rossi, Mario
Meister, Jaroslawna
Inoue, Asuka
Beck-Sickinger, Annette G.
Gurevich, Vsevolod V.
Wess, Juergen
TI A G Protein-biased Designer G Protein-coupled Receptor Useful for
Studying the Physiological Relevance of G(q/11)-dependent Signaling
Pathways
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE 7-helix receptor; arrestin; cell signaling; G protein; G protein-coupled
receptor (GPCR); DREADD; biased signaling
ID IN-VIVO; FUNCTIONAL SELECTIVITY; NONVISUAL ARRESTINS; LIPID-METABOLISM;
STRUCTURAL BASIS; INSULIN-RELEASE; ACTIVATION; DESENSITIZATION;
RESIDUES; AGONISM
AB Designer receptors exclusively activated by a designer drug (DREADDs) are clozapine-N-oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs, clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger -arrestin-dependent (G protein-independent) signaling. To dissect the relative physiological relevance of G protein-mediated versus -arrestin-mediated signaling in different cell types or physiological processes, the availability of G protein- and -arrestin-biased DREADDs would be highly desirable. In this study, we report the development of a mutationally modified version of a non-biased DREADD derived from the M-3 muscarinic receptor that can activate G(q/11) with high efficacy but lacks the ability to interact with -arrestins. We also demonstrate that this novel DREADD is active in vivo and that cell type-selective expression of this new designer receptor can provide novel insights into the physiological roles of G protein (G(q/11))-dependent versus -arrestin-dependent signaling in hepatocytes. Thus, this novel G(q/11)-biased DREADD represents a powerful new tool to study the physiological relevance of G(q/11)-dependent signaling in distinct tissues and cell types, in the absence of -arrestin-mediated cellular effects. Such studies should guide the development of novel classes of functionally biased ligands that show high efficacy in various pathophysiological conditions but display a reduced incidence of side effects.
C1 [Hu, Jianxin; Stern, Matthew; Zhu, Lu; Rossi, Mario; Meister, Jaroslawna; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA.
[Gimenez, Luis E.; Gurevich, Vsevolod V.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
[Wanka, Lizzy; Beck-Sickinger, Annette G.] Univ Leipzig, Inst Biochem, D-04103 Leipzig, Germany.
[Inoue, Asuka] Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi 9808578, Japan.
[Inoue, Asuka] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
RI Gurevich, Vsevolod/A-3236-2008
OI Gurevich, Vsevolod/0000-0002-3950-5351
FU National Institutes of Health Intramural Research Program; NIDDK; United
States Department of Health and Human Services; Deutsche
Forschungsgemeinschaft [DCRC1052-A3]; National Institutes of Health
[GM077561, GM109955]; PRESTO, Japan Science and Technology Agency
FX This work was supported by the National Institutes of Health Intramural
Research Program, NIDDK, United States Department of Health and Human
Services (to J. H., M. S., L. Z., M. R., J. M., and J. W.), Deutsche
Forschungsgemeinschaft Grant DCRC1052-A3 (to L. W.), National Institutes
of Health RO1 Grants GM077561 and GM109955 (to V. V. G.), and PRESTO,
Japan Science and Technology Agency (to A. I.). The authors declare that
they have no conflicts of interest with the contents of this article.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 50
TC 1
Z9 1
U1 2
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 8
PY 2016
VL 291
IS 15
BP 7809
EP 7820
DI 10.1074/jbc.M115.702282
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ2SZ
UT WOS:000374056700005
PM 26851281
ER
PT J
AU Fan, MH
Zhu, Q
Li, HH
Ra, HJ
Majumdar, S
Gulick, DL
Jerome, JA
Madsen, DH
Christofidou-Solomidou, M
Speicher, DW
Bachovchin, WW
Feghali-Bostwick, C
Pure, E
AF Fan, Ming-Hui
Zhu, Qiang
Li, Hui-Hua
Ra, Hyun-Jeong
Majumdar, Sonali
Gulick, Dexter L.
Jerome, Jacob A.
Madsen, Daniel H.
Christofidou-Solomidou, Melpo
Speicher, David W.
Bachovchin, William W.
Feghali-Bostwick, Carol
Pure, Ellen
TI Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and
Clearance from Lungs in Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE collagen; extracellular matrix; fibroblast; pulmonary fibrosis; serine
protease; gelatinase; interstitial lung disease
ID IDIOPATHIC PULMONARY-FIBROSIS; SERINE-PROTEASE; EXTRACELLULAR-MATRIX;
STROMAL FIBROBLASTS; PROTEOLYTIC ACTIVATION; PROCOLLAGEN PRODUCTION;
REMODELING INTERFACE; NEUTROPHIL ELASTASE; TISSUE INHIBITORS;
TUMOR-GROWTH
AB Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung.
C1 [Fan, Ming-Hui; Li, Hui-Hua; Gulick, Dexter L.; Jerome, Jacob A.] Univ Pittsburgh, Dept Med, Pulm Allergy & Crit Care Div, 930 Scaife Hall, Pittsburgh, PA 15213 USA.
[Zhu, Qiang] Univ N Carolina, Mol & Cellular Pathol Grad Program, Chapel Hill, NC 27599 USA.
[Ra, Hyun-Jeong; Christofidou-Solomidou, Melpo] Univ Penn, Dept Hematol & Oncol, Philadelphia, PA 19104 USA.
[Pure, Ellen] Univ Penn, Dept Biomed Sci, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA.
[Pure, Ellen] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA.
[Majumdar, Sonali; Speicher, David W.] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Madsen, Daniel H.] NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, Ctr Canc Immune Therapy,NIH, Bethesda, MD 20892 USA.
[Bachovchin, William W.] Tufts Univ, Sackler Sch Biomed Grad Sci, Boston, MA 02111 USA.
[Feghali-Bostwick, Carol] Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA.
RP Fan, MH (reprint author), Univ Pittsburgh, Dept Med, Pulm Allergy & Crit Care Div, 930 Scaife Hall, Pittsburgh, PA 15213 USA.
EM fanm@upmc.edu
OI Madsen, Daniel Hargboel/0000-0002-3183-6201
FU National Institutes of Health [R01 CA141144, R01 CA133470, K08HL102266,
P30AR05891, K24 AR060297, R01 CA131582]; Dalsemer Research Award from
the American Lung Association [DA167003]; Intramural Research Program of
the National Institutes of Health from NIDCR; NCI [P30 CA010815]
FX This work was supported by National Institutes of Health Grants R01
CA141144 (to E. P.), R01 CA133470 (to M. C. S.), K08HL102266 (to M. H.
F.), P30AR05891 (to PI Mark Gladwin; funding provided to M. H. F.), and
K24 AR060297 (to C. F. B.), Dalsemer Research Award DA167003 (M. H. F.)
from the American Lung Association, and in part by the Intramural
Research Program of the National Institutes of Health from NIDCR (to D.
H. M.), National Institutes of Health Grant R01 CA131582 (to D. W. S.),
and Core Grant P30 CA010815 from NCI (to The Wistar Institute). M. C. S.
has patents PCT/US14/41636 and PCT/US15/22501 pending and has a
founder's equity position in LignaMed, LLC, but these have no connection
to the data reported in this article. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 75
TC 2
Z9 2
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 8
PY 2016
VL 291
IS 15
BP 8070
EP 8089
DI 10.1074/jbc.M115.701433
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ2SZ
UT WOS:000374056700026
PM 26663085
ER
PT J
AU Varmus, H
AF Varmus, Harold
TI The transformation of oncology
SO SCIENCE
LA English
DT Editorial Material
C1 [Varmus, Harold] Weill Cornell Med, Meyer Canc Ctr, New York, NY USA.
[Varmus, Harold] US Natl Canc Inst, Rockville, MD 20850 USA.
RP Varmus, H (reprint author), Weill Cornell Med, Meyer Canc Ctr, New York, NY USA.; Varmus, H (reprint author), US Natl Canc Inst, Rockville, MD 20850 USA.
EM varmus@med.cornell.edu
NR 0
TC 0
Z9 0
U1 20
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD APR 8
PY 2016
VL 352
IS 6282
BP 123
EP 123
DI 10.1126/science.aaf7301
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI7LM
UT WOS:000373681600001
PM 27124426
ER
PT J
AU Churchman, ML
Evans, K
Richmond, J
Robbins, A
Jones, L
Shapiro, IM
Pachter, JA
Weaver, DT
Houghton, PJ
Smith, MA
Lock, RB
Mullighan, CG
AF Churchman, Michelle L.
Evans, Kathryn
Richmond, Jennifer
Robbins, Alissa
Jones, Luke
Shapiro, Irina M.
Pachter, Jonathan A.
Weaver, David T.
Houghton, Peter J.
Smith, Malcolm A.
Lock, Richard B.
Mullighan, Charles G.
TI Synergism of FAK and tyrosine kinase inhibition in Ph+ B-ALL
SO JCI INSIGHT
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FOCAL ADHESION KINASE; GENETIC
ALTERATIONS; MOUSE MODEL; BCR-ABL; IKAROS; IMATINIB; CELLS;
HAPLOINSUFFICIENCY; PHOSPHORYLATION
AB BCR-ABL1(+) B progenitor acute lymphoblastic leukemia (Ph+ B-ALL) is an aggressive disease that frequently responds poorly to currently available therapies. Alterations in IKZF1, which encodes the lymphoid transcription factor Ikaros, are present in over 80% of Ph+ ALL and are associated with a stem cell-like phenotype, aberrant adhesion molecule expression and signaling, leukemic cell adhesion to the bone marrow stem cell niche, and poor outcome. Here, we show that FAK1 is upregulated in Ph+ B-ALL with further overexpression in IKZF1-altered cells and that the FAK inhibitor VS-4718 potently inhibits aberrant FAK signaling and leukemic cell adhesion, potentiating responsiveness to tyrosine kinase inhibitors, inducing cure in vivo. Thus, targeting FAK with VS-4718 is an attractive approach to overcome the deleterious effects of FAK overexpression in Ph+ B-ALL, particularly in abrogating the adhesive phenotype induced by Ikaros alterations, and warrants evaluation in clinical trials for Ph+ B-ALL, regardless of IKZF1 status.
C1 [Churchman, Michelle L.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Evans, Kathryn; Richmond, Jennifer; Robbins, Alissa; Jones, Luke; Lock, Richard B.] Univ New South Wales, Lowy Canc Res Ctr, Childrens Canc Inst, Sydney, NSW, Australia.
[Shapiro, Irina M.; Pachter, Jonathan A.; Weaver, David T.] Verastem Inc, Needham, MA USA.
[Houghton, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Mullighan, CG (reprint author), St Jude Childrens Res Hosp, Pathol, 262 Danny Thomas Pl,Mail Stop 342, Memphis, TN 38105 USA.
EM charles.mullighan@stjude.org
RI Lock, Richard/G-4253-2013
NR 38
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD APR 7
PY 2016
VL 1
IS 4
AR e86082
DI 10.1172/jci.insight.86082
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1IU
UT WOS:000387104400005
ER
PT J
AU Kozlenkov, A
Wang, MH
Roussos, P
Rudchenko, S
Barbu, M
Bibikova, M
Klotzle, B
Dwork, AJ
Zhang, B
Hurd, YL
Koonin, EV
Wegner, M
Dracheva, S
AF Kozlenkov, Alexey
Wang, Minghui
Roussos, Panos
Rudchenko, Sergei
Barbu, Mihaela
Bibikova, Marina
Klotzle, Brandy
Dwork, Andrew J.
Zhang, Bin
Hurd, Yasmin L.
Koonin, Eugene V.
Wegner, Michael
Dracheva, Stella
TI Substantial DNA methylation differences between two major neuronal
subtypes in human brain
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HUMAN HOUSEKEEPING GENES; RETT-SYNDROME; GABAERGIC
INTERNEURONS; EPIGENETIC MEMORY; PREFRONTAL CORTEX; SITE RESOLUTION;
MECP2 BINDS; RNA-SEQ; SCHIZOPHRENIA
AB The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons-GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.
C1 [Kozlenkov, Alexey; Roussos, Panos; Dracheva, Stella] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Kozlenkov, Alexey; Roussos, Panos; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
[Kozlenkov, Alexey; Roussos, Panos; Hurd, Yasmin L.; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Wang, Minghui; Roussos, Panos; Zhang, Bin] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Rudchenko, Sergei; Barbu, Mihaela] Hosp Special Surg, New York, NY 10021 USA.
[Bibikova, Marina; Klotzle, Brandy] Illumina Inc, San Diego, CA 92122 USA.
[Dwork, Andrew J.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Wegner, Michael] Univ Erlangen Nurnberg, Emil Fischer Zentrum, Inst Biochem, D-91054 Erlangen, Germany.
RP Dracheva, S (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA.; Dracheva, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.; Dracheva, S (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
EM Stella.Dracheva@mssm.edu
RI Roussos, Panos/J-7090-2013
OI Roussos, Panos/0000-0002-4640-6239
FU National Institute of Mental Health [R21MH103877]; U.S. Department of
Veterans Affairs [BX001829]; U.S. Department of Health and Human
Services; National Institute of Health
FX National Institute of Mental Health [R21MH103877 that is a part of the
PsychENCODE consortium to S.D.]; U.S. Department of Veterans Affairs
[Merit Review Award BX001829 to S.D.]; Intramural funds of the U.S.
Department of Health and Human Services to National Library of Medicine
(to E.V.K.). Funding for open access charge: National Institute of
Health.
NR 96
TC 7
Z9 7
U1 5
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 7
PY 2016
VL 44
IS 6
BP 2593
EP 2612
DI 10.1093/nar/gkv1304
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ9YW
UT WOS:000374570500020
PM 26612861
ER
PT J
AU Dahmane, N
Gadelle, D
Delmas, S
Criscuolo, A
Eberhard, S
Desnoues, N
Collin, S
Zhang, HL
Pommier, Y
Forterre, P
Sezonov, G
AF Dahmane, Narimane
Gadelle, Daniele
Delmas, Stephane
Criscuolo, Alexis
Eberhard, Stephan
Desnoues, Nicole
Collin, Sylvie
Zhang, Hongliang
Pommier, Yves
Forterre, Patrick
Sezonov, Guennadi
TI toplb, a phylogenetic hallmark gene of Thaumarchaeota encodes a
functional eukaryote- like topoisomerase IB
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID AMMONIA-OXIDIZING ARCHAEON; DNA TOPOISOMERASE;
NITROSOSPHAERA-VIENNENSIS; CLEAVAGE COMPLEXES; VACCINIA VIRUS;
CAMPTOTHECIN; MECHANISM; SEQUENCE; ORIGIN; INHIBITORS
AB Type IB DNA topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thaumarchaeota. However, the activities and the roles of these topoisomerases have remained an open question. Here, we demonstrate that all available thaumarchaeal genomes contain a topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Nitrososphaera viennensis and we purified the recombinant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described thermostable topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies.
C1 [Dahmane, Narimane; Delmas, Stephane; Eberhard, Stephan; Collin, Sylvie; Sezonov, Guennadi] Univ Paris 06, Unite Evolut Paris Seine UMR 7138, Sorbonne Univ, IBPS,CNRS, F-75005 Paris, France.
[Gadelle, Daniele; Forterre, Patrick] Univ Paris Saclay, Univ Paris 11, CNRS, I2BC,CEA, F-91198 Gif Sur Yvette, France.
[Criscuolo, Alexis] USR 3756 IP CNRS, Inst Pasteur, Hub Bioinformat & Biostat C3BI, 25-28 Rue Docteur Roux, F-75724 Paris 15, France.
[Desnoues, Nicole; Forterre, Patrick] Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, Dept Microbiol, 25-28 Rue Docteur Roux, F-75724 Paris 15, France.
[Zhang, Hongliang; Pommier, Yves] NCI, Mol Pharmacol Lab, Dev Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Sezonov, G (reprint author), Univ Paris 06, Unite Evolut Paris Seine UMR 7138, Sorbonne Univ, IBPS,CNRS, F-75005 Paris, France.; Forterre, P (reprint author), Univ Paris Saclay, Univ Paris 11, CNRS, I2BC,CEA, F-91198 Gif Sur Yvette, France.; Forterre, P (reprint author), Inst Pasteur, Unit Biol Mol Gene Chez Extremophiles, Dept Microbiol, 25-28 Rue Docteur Roux, F-75724 Paris 15, France.; Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Dev Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov; forterre@pasteur.fr; guennadi.sezonov@courriel.upmc.fr
FU LabeX 'Initiative d'Excellence' program [ANR-11-LABX-0011-01]; NCI
Intramural Program, Center for Cancer Research [BC-006161]; Institut
Pasteur
FX LabeX 'Initiative d'Excellence' program [Grant 'DYNAMO,'
ANR-11-LABX-0011-01]; NCI Intramural Program, Center for Cancer Research
[BC-006161]. Funding for open access charge: Institut Pasteur.
NR 59
TC 0
Z9 0
U1 3
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR 7
PY 2016
VL 44
IS 6
BP 2795
EP 2805
DI 10.1093/nar/gkw097
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ9YW
UT WOS:000374570500033
PM 26908651
ER
PT J
AU Kuschal, C
Botta, E
Orioli, D
Digiovanna, JJ
Seneca, S
Keymolen, K
Tamura, D
Heller, E
Khan, SG
Caligiuri, G
Lanzafame, M
Nardo, T
Ricotti, R
Peverali, FA
Stephens, R
Zhao, YM
Lehmann, AR
Baranello, L
Levens, D
Kraemer, KH
Stefanini, M
AF Kuschal, Christiane
Botta, Elena
Orioli, Donata
Digiovanna, John J.
Seneca, Sara
Keymolen, Kathelijn
Tamura, Deborah
Heller, Elizabeth
Khan, Sikandar G.
Caligiuri, Giuseppina
Lanzafame, Manuela
Nardo, Tiziana
Ricotti, Roberta
Peverali, Fiorenzo A.
Stephens, Robert
Zhao, Yongmei
Lehmann, Alan R.
Baranello, Laura
Levens, David
Kraemer, Kenneth H.
Stefanini, Miria
TI GTF2E2 Mutations Destabilize the General Transcription Factor Complex
TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID RNA-POLYMERASE-II; GENOTYPE-PHENOTYPE RELATIONSHIPS; C7ORF11 TTDN1 GENE;
XERODERMA-PIGMENTOSUM; BASAL TRANSCRIPTION; XPD MUTATIONS;
EXCISION-REPAIR; BETA-SUBUNIT; DISORDER TRICHOTHIODYSTROPHY;
COCKAYNE-SYNDROME
AB The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.A1a150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIE beta). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIE alpha and TFIIE beta) as well as decreased phosphorylation of TFIIE alpha in cells from both children. Interestingly, decreased phosphorylation of TFIIE alpha was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP.
C1 [Kuschal, Christiane; Digiovanna, John J.; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Botta, Elena; Orioli, Donata; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A.; Stefanini, Miria] CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy.
[Seneca, Sara; Keymolen, Kathelijn] Vrije Univ Brussel, UZ Brussel, Res Grp Reprod & Genet, Ctr Med Genet, Laarbeeklaan 101, B-1090 Brussels, Belgium.
[Stephens, Robert] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Cancer Res Technol Program, Frederick, MD 21702 USA.
[Stephens, Robert; Zhao, Yongmei] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Lehmann, Alan R.] Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
[Baranello, Laura; Levens, David] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kuschal, Christiane] Natl Univ Singapore, Canc Sci Inst, 14 Med Dr, Singapore 117599, Singapore.
RP Kraemer, KH (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.; Stefanini, M (reprint author), CNR, Ist Genet Mol, Via Abbiategrasso 207, I-27100 Pavia, Italy.
EM kraemerk@nih.gov; stefanini@igm.cnr.it
OI Kuschal, Christiane/0000-0001-6113-3585; BOTTA,
ELENA/0000-0003-2060-0110
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Associazione Italiana per la Ricerca sul
Cancro Grant [IG 13537, IG 17710]; Telethon Grant [GEP13022]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research (C.K.,
K.H.K., J.J.D., S.G.K., D.T., D.L., L.B., R.S.), the Associazione
Italiana per la Ricerca sul Cancro Grant IG 13537 (M.S.), and IG 17710
(D.O.) and Telethon Grant GEP13022 (E.B.). We thank Dr. Wei Yang (NIDDK,
NIH) for the schematic image of TFIIE mutations, Russell Bandle (NCI)
for helpful suggestions in the procedure of nuclear protein isolation,
and Heather Fawcett (Sussex University) for technical assistance. We
would also like to thank the Genomics Laboratory and CCR Sequencing
Facility at Frederick National Laboratory for Cancer Research including
Dan Soppett and Kristen Pike for DNA target preparation, Bao Tran for
performing the sequencing, Ming Yi for help perfecting the GATK
workflow, and Shashi Ratanayke and Keyur Talsania for assistance running
the analysis.
NR 62
TC 0
Z9 0
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 7
PY 2016
VL 98
IS 4
BP 627
EP 642
DI 10.1016/j.ajhg.2016.02.008
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ4UO
UT WOS:000374203800003
PM 26996949
ER
PT J
AU Chen, H
Wang, CL
Conomos, MP
Stilp, AM
Li, ZL
Sofer, T
Szpiro, AA
Chen, W
Brehm, JM
Celedon, JC
Redline, S
Papanicolaou, GJ
Thornton, TA
Laurie, CC
Rice, K
Lin, XH
AF Chen, Han
Wang, Chaolong
Conomos, Matthew P.
Stilp, Adrienne M.
Li, Zilin
Sofer, Tamar
Szpiro, Adam A.
Chen, Wei
Brehm, John M.
Celedon, Juan C.
Redline, Susan
Papanicolaou, George J.
Thornton, Timothy A.
Laurie, Cathy C.
Rice, Kenneth
Lin, Xihong
TI Control for Population Structure and Relatedness for Binary Traits in
Genetic Association Studies via Logistic Mixed Models
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; STRATIFICATION; POWER; LOCI;
LATINOS; SUSCEPTIBILITY; REGRESSION; DISEASE; TESTS
AB Linear mixed models (LMMs) are widely used in genome-wide association studies (GWASs) to account for population structure and relatedness, for both continuous and binary traits. Motivated by the failure of LMMs to control type I errors in a GWAS of asthma, a binary trait, we show that LMMs are generally inappropriate for analyzing binary traits when population stratification leads to violation of the LMM's constant-residual variance assumption. To overcome this problem, we develop a computationally efficient logistic mixed model approach for genome-wide analysis of binary traits, the generalized linear mixed model association test (GMMAT). This approach fits a logistic mixed model once per GWAS and performs score tests under the null hypothesis of no association between a binary trait and individual genetic variants. We show in simulation studies and real data analysis that GMMAT effectively controls for population structure and relatedness when analyzing binary traits in a wide variety of study designs.
C1 [Chen, Han; Wang, Chaolong; Li, Zilin; Lin, Xihong] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Wang, Chaolong] Genome Inst Singapore, Computat & Syst Biol, Singapore 138672, Singapore.
[Conomos, Matthew P.; Stilp, Adrienne M.; Sofer, Tamar; Szpiro, Adam A.; Thornton, Timothy A.; Laurie, Cathy C.; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Li, Zilin] Tsinghua Univ, Dept Math, Beijing 100084, Peoples R China.
[Chen, Wei; Brehm, John M.; Celedon, Juan C.] Univ Pittsburgh, UPMC, Childrens Hosp Pittsburgh, Div Pediat Pulm Med Allergy & Immunol, Pittsburgh, PA 15224 USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med & Neurol, Div Sleep & Circadian Disorders, Boston, MA 02115 USA.
[Papanicolaou, George J.] NHLBI, Prevent & Populat Sci Program, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Lin, XH (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM xlin@hsph.harvard.edu
OI Chen, Han/0000-0002-9510-4923; Sofer, Tamar/0000-0001-8520-8860
FU China Scholarship Council; National Heart, Lung, and Blood Institute
(NHLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert
Einstein College of Medicine [N01-HC65235]; Northwestern University
[N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI: National
Institute on Minority Health and Health Disparities; National Institute
on Deafness and Other Communication Disorders; National Institute of
Dental and Craniofacial Research (NIDCR); National Institute of Diabetes
and Digestive and Kidney Diseases; National Institute of Neurological
Disorders and Stroke; NIH Office of Dietary Supplements; NIDCR
[HHSN268201300005C AM03, MOD03]; NHLBI [HSN26220/20054C]; National
Center for Advancing Translational Science Clinical Translational
Science Institute [UL1TR000124]; NIDDK Diabetes Research Center
[DK063491]; [P01 CA134294]; [R35 CA197449]; [R01 HL113338]; [K99
HL130593]; [R37 CA076404]
FX This work was supported by grants P01 CA134294, R35 CA197449, and R01
HL113338 (to H.C., Z.L., and X.L.), K99 HL130593 (to H.C.), and R37
CA076404 (to C.W., Z.L., and X.L.). Z.L. was also supported in part by a
scholarship from the China Scholarship Council. We thank the
participants and staff of the Hispanic Community Health Study/Study of
Latinos (HCHS/SOL) for their contributions to this study. The baseline
examination of HCHS/SOL was carried out as a collaborative study
supported by contracts from the National Heart, Lung, and Blood
Institute (NHLBI) to the University of North Carolina (N01-HC65233),
University of Miami (N01-HC65234), Albert Einstein College of Medicine
(N01-HC65235), Northwestern University (N01-HC65236), and San Diego
State University (N01-HC65237). The following institutes, centers, and
offices contributed to the first phase of HCHS/SOL through a transfer of
funds to the NHLBI: National Institute on Minority Health and Health
Disparities, National Institute on Deafness and Other Communication
Disorders, National Institute of Dental and Craniofacial Research
(NIDCR), National Institute of Diabetes and Digestive and Kidney
Diseases, National Institute of Neurological Disorders and Stroke, and
NIH Office of Dietary Supplements. The Genetic Analysis Center at the
University of Washington was supported by NHLBI and NIDCR contracts
(HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by
NHLBI (HSN26220/20054C), National Center for Advancing Translational
Science Clinical Translational Science Institute (UL1TR000124), and
NIDDK Diabetes Research Center (DK063491). This manuscript has been
reviewed by the HCHS/SOL Publications Committee for scientific content
and consistency of data interpretation with previous HCHS/SOL
publications.
NR 38
TC 7
Z9 7
U1 4
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 7
PY 2016
VL 98
IS 4
BP 653
EP 666
DI 10.1016/j.ajhg.2016.02.012
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ4UO
UT WOS:000374203800005
PM 27018471
ER
PT J
AU Joubert, BR
Felix, JF
Yousefi, P
Bakulski, KM
Just, AC
Breton, C
Reese, SE
Markunas, CA
Richmond, RC
Xu, CJ
Kupers, LK
Oh, SS
Hoyo, C
Gruzieva, O
Soderhal, C
Salas, LA
Baiz, N
Zhang, HM
Lepeule, J
Ruiz, C
Ligthart, S
Wang, TY
Taylor, JA
Duijts, L
Sharp, GC
Jankipersadsing, SA
Nilsen, RM
Vaez, A
Fallin, MD
Hu, DL
Litonjua, AA
Fuemmeler, BF
Huen, K
Kere, J
Kull, I
Munthe-Kaas, MC
Gehring, U
Bustamante, M
Saurel-Coubizolles, MJ
Quraishi, BM
Ren, J
Tost, J
Gonzalez, JR
Peters, MJ
Haberg, SE
Xu, ZL
van Meurs, JB
Gaunt, TR
Kerkhof, M
Corpeleijn, E
Feinberg, AP
Eng, C
Baccarelli, AA
Neelon, SEB
Bradman, A
Merid, SK
Bergstrom, A
Herceg, Z
Hernandez-Vargas, H
Brunekreef, B
Pinart, M
Heude, B
Ewart, S
Yao, J
Lemonnier, N
Franco, OH
Wu, MC
Hofman, A
McArdle, W
Van der Vlies, P
Falahi, F
Gillman, MW
Barcellos, LF
Kumar, A
Wickman, M
Guerra, S
Charles, MA
Holloway, J
Auffray, C
Tiemeier, HW
Smith, GD
Postma, D
Hivert, MF
Eskenazi, B
Vrijheid, M
Arshad, H
Anto, JM
Dehghan, A
Karmaus, W
Annesi-Maesano, I
Sunyer, J
Ghantous, A
Pershagen, G
Hollands, N
Murphy, SK
DeMeo, DL
Burchard, EG
Ladd-Acosta, C
Snieder, H
Nystad, W
Koppelman, GH
Relton, CL
Jaddoe, VWV
Wilcox, A
Melen, E
London, SJ
AF Joubert, Bonnie R.
Felix, Janine F.
Yousefi, Paul
Bakulski, Kelly M.
Just, Allan C.
Breton, Carrie
Reese, Sarah E.
Markunas, Christina A.
Richmond, Rebecca C.
Xu, Cheng-Jian
Kupers, Leanne K.
Oh, Sam S.
Hoyo, Cathrine
Gruzieva, Olena
Soderhal, Cilla
Salas, Lucas A.
Baiz, Nour
Zhang, Hongmei
Lepeule, Johanna
Ruiz, Carlos
Ligthart, Symen
Wang, Tianyuan
Taylor, Jack A.
Duijts, Liesbeth
Sharp, Gemma C.
Jankipersadsing, Soesma A.
Nilsen, Roy M.
Vaez, Ahmad
Fallin, M. Daniele
Hu, Donglei
Litonjua, Augusto A.
Fuemmeler, Bernard F.
Huen, Karen
Kere, Juha
Kull, Inger
Munthe-Kaas, Monica Cheng
Gehring, Ulrike
Bustamante, Mariona
Saurel-Coubizolles, Marie Jose
Quraishi, Bilal M.
Ren, Jie
Tost, Jorg
Gonzalez, Juan R.
Peters, Marjolein J.
Haberg, Siri E.
Xu, Zongli
van Meurs, Joyce B.
Gaunt, Tom R.
Kerkhof, Marjan
Corpeleijn, Eva
Feinberg, Andrew P.
Eng, Celeste
Baccarelli, Andrea A.
Neelon, Sara E. Benjamin
Bradman, Asa
Merid, Simon Kebede
Bergstrom, Anna
Herceg, Zdenko
Hernandez-Vargas, Hector
Brunekreef, Bert
Pinart, Mariona
Heude, Barbara
Ewart, Susan
Yao, Jin
Lemonnier, Nathanael
Franco, Oscar H.
Wu, Michael C.
Hofman, Albert
McArdle, Wendy
Van der Vlies, Pieter
Falahi, Fahimeh
Gillman, Matthew W.
Barcellos, Lisa F.
Kumar, Ashish
Wickman, Magnus
Guerra, Stefano
Charles, Marie-Aline
Holloway, John
Auffray, Charles
Tiemeier, Henning W.
Smith, George Davey
Postma, Dirkje
Hivert, Marie-France
Eskenazi, Brenda
Vrijheid, Martine
Arshad, Hasan
Anto, Josep M.
Dehghan, Abbas
Karmaus, Wilfried
Annesi-Maesano, Isabella
Sunyer, Jordi
Ghantous, Akram
Pershagen, Goran
Hollands, Nina
Murphy, Susan K.
DeMeo, Dawn L.
Burchard, Esteban G.
Ladd-Acosta, Christine
Snieder, Harold
Nystad, Wenche
Koppelman, Gerard H.
Relton, Caroline L.
Jaddoe, Vincent W. V.
Wilcox, Allen
Melen, Erik
London, Stephanie J.
TI DNA Methylation in Newborns and Maternal Smoking in Pregnancy:
Genome-wide Consortium Meta-analysis
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID HYDROCARBON RECEPTOR REPRESSOR; AUTISM SPECTRUM DISORDERS; LYMPH-NODE
METASTASIS; LUNG-FUNCTION DECLINE; CIGARETTE-SMOKING; NEUROPILIN-2
EXPRESSION; BREAST-CANCER; IN-UTERO; POSTSYNAPTIC DENSITY; PRENATAL
EXPOSURE
AB Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 x 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
C1 [Joubert, Bonnie R.; Reese, Sarah E.; Markunas, Christina A.; Wang, Tianyuan; Taylor, Jack A.; Xu, Zongli] NIEHS, NIH, US Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
[Felix, Janine F.; Ligthart, Symen; Duijts, Liesbeth; Franco, Oscar H.; Dehghan, Abbas] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Felix, Janine F.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, NL-3000 CA Rotterdam, Netherlands.
[Felix, Janine F.; Duijts, Liesbeth; Tiemeier, Henning W.] Univ Med Ctr Rotterdam, Erasmus MC, Generat Study Grp R, NL-3000 CA Rotterdam, Netherlands.
[Yousefi, Paul; Huen, Karen; Bradman, Asa; Barcellos, Lisa F.; Eskenazi, Brenda] Univ Calif Berkeley, Sch Publ Hlth, CERCH, Berkeley, CA 94720 USA.
[Bakulski, Kelly M.; Fallin, M. Daniele; Neelon, Sara E. Benjamin] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Just, Allan C.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
[Breton, Carrie; Ren, Jie; Yao, Jin] Univ So Calif, Los Angeles, CA 90032 USA.
[Markunas, Christina A.] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC 27710 USA.
[Richmond, Rebecca C.; Sharp, Gemma C.; Gaunt, Tom R.; Smith, George Davey; Relton, Caroline L.] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Xu, Cheng-Jian; Jankipersadsing, Soesma A.; Van der Vlies, Pieter] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[Xu, Cheng-Jian; Jankipersadsing, Soesma A.; Postma, Dirkje] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, NL-9700 RB Groningen, Netherlands.
[Xu, Cheng-Jian; Kerkhof, Marjan; Postma, Dirkje; Koppelman, Gerard H.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst Groningen, NL-9700 RB Groningen, Netherlands.
[Kupers, Leanne K.; Vaez, Ahmad; Corpeleijn, Eva; Falahi, Fahimeh; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
[Oh, Sam S.; Hu, Donglei; Eng, Celeste; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Hoyo, Cathrine] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Hoyo, Cathrine] N Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC 27695 USA.
[Gruzieva, Olena; Kull, Inger; Merid, Simon Kebede; Bergstrom, Anna; Kumar, Ashish; Wickman, Magnus; Pershagen, Goran; Melen, Erik] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
[Soderhal, Cilla; Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden.
[Salas, Lucas A.; Ruiz, Carlos; Bustamante, Mariona; Gonzalez, Juan R.; Pinart, Mariona; Guerra, Stefano; Vrijheid, Martine; Anto, Josep M.; Sunyer, Jordi] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain.
[Salas, Lucas A.; Ruiz, Carlos; Bustamante, Mariona; Gonzalez, Juan R.; Pinart, Mariona; Vrijheid, Martine; Anto, Josep M.; Sunyer, Jordi] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08003, Spain.
[Salas, Lucas A.; Ruiz, Carlos; Bustamante, Mariona; Gonzalez, Juan R.; Pinart, Mariona; Vrijheid, Martine; Anto, Josep M.; Sunyer, Jordi] UPF, Barcelona 08003, Spain.
[Baiz, Nour; Annesi-Maesano, Isabella] Univ Paris 06, Sorbonne Univ,St Antoine Med Sch, INSERM,Epidemiol Allerg & Resp Dis Dept EPAR, Pierre Louis Inst Epidemiol & Publ Hlth IPLESP UM, F-75012 Paris, France.
[Zhang, Hongmei; Quraishi, Bilal M.; Karmaus, Wilfried] Univ Memphis, Sch Publ Hlth, Div Epidemiol Biostat & Environm Hlth, Memphis, TN 38152 USA.
[Lepeule, Johanna] Univ Grenoble, Ctr Hosp, Univ Grenoble Alpes,Team Environm Epidemiol Appl, Inst Natl Sante & Rech Med,Inst Albert Bonniot, F-38000 Grenoble, France.
[Duijts, Liesbeth] Univ Med Ctr Rotterdam, Erasmus MC, Div Neonatol, Dept Pediat, NL-3000 CA Rotterdam, Netherlands.
[Duijts, Liesbeth] Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Div Resp Med, NL-3000 CA Rotterdam, Netherlands.
[Nilsen, Roy M.] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway.
[Vaez, Ahmad] Isfahan Univ Med Sci, Sch Med, Esfahan 8174673461, Iran.
[Litonjua, Augusto A.; DeMeo, Dawn L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Fuemmeler, Bernard F.] Duke Univ, Sch Med, Dept Community & Family Med, Durham, NC 27710 USA.
[Munthe-Kaas, Monica Cheng] Oslo Univ Hosp, Dept Pediat, N-424 Oslo, Norway.
[Gehring, Ulrike; Brunekreef, Bert] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
[Bustamante, Mariona] Ctr Genom Regulat CRG, Barcelona 08003, Spain.
[Saurel-Coubizolles, Marie Jose] INSERM, Epidemiol Res Unit Perinatal Hlth & Womens & Chil, F-75654 Paris, France.
[Tost, Jorg] CEA, Inst Genom, Ctr Natl Genotypage, Lab Epigenet & Environm, F-91000 Evry, France.
[Peters, Marjolein J.; van Meurs, Joyce B.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Haberg, Siri E.; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, N-0403 Oslo, Norway.
[Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Baccarelli, Andrea A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Herceg, Zdenko; Hernandez-Vargas, Hector; Ghantous, Akram] IARC, Epigenet Grp, F-69008 Lyon, France.
[Brunekreef, Bert] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 TD Utrecht, Netherlands.
[Pinart, Mariona; Anto, Josep M.; Sunyer, Jordi] Hosp Mar Med Res Inst IMIM, Barcelona 08003, Spain.
[Heude, Barbara; Charles, Marie-Aline] Univ Paris 05, INSERM, UMR 1153,Ctr Rech Epidemiol & Stat Sorbonne Paris, Early Origin Childs Hlth & Dev ORCHAD Team, F-94807 Villejuif, France.
[Ewart, Susan] Michigan State Univ, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA.
[Lemonnier, Nathanael; Auffray, Charles] Univ Lyon 1, Ctr Natl Rech Sci, Ecole Normale Super, European Inst Syst Biol & Med, F-69007 Lyon, France.
[Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Hofman, Albert] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[McArdle, Wendy] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England.
[Gillman, Matthew W.; Hivert, Marie-France] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA 02215 USA.
[Gillman, Matthew W.; Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.
[Kumar, Ashish] Swiss Trop & Publ Hlth Inst, Unit Chron Dis Epidemiol, Dept Publ Hlth Epidemiol, CH-4051 Basel, Switzerland.
[Kumar, Ashish] Univ Basel, CH-4001 Basel, Switzerland.
[Wickman, Magnus; Melen, Erik] Stockholm Cty Council, Sachs Childrens Hosp, S-17177 Stockholm, Sweden.
[Wickman, Magnus; Melen, Erik] Stockholm Cty Council, Ctr Occupat & Environm Med, S-17177 Stockholm, Sweden.
[Holloway, John; Arshad, Hasan] Univ Southampton, Fac Med Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
[Holloway, John] Univ Southampton, Fac Med Human Dev & Hlth, Southampton SO16 6YD, Hants, England.
[Murphy, Susan K.] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Murphy, Susan K.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA.
[Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Koppelman, Gerard H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp, NL-9700 RB Groningen, Netherlands.
RP London, SJ (reprint author), NIEHS, NIH, US Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
RI Pinart, Mariona/L-1931-2015; Anto, J/H-2676-2014; Annesi-Maesano,
Isabella/D-9173-2016; Holloway, John/B-5424-2009; LEPEULE,
Johanna/K-1085-2016; Gaunt, Tom/O-3918-2014; Heude, Barbara/G-3095-2016;
Kere, Juha/A-9179-2008; Sunyer, J/G-6909-2014; Davey Smith,
George/A-7407-2013; GHANTOUS, Akram/C-1689-2017; Vrijheid, M/H-2702-2014
OI Just, Allan/0000-0003-4312-5957; Dehghan, Abbas/0000-0001-6403-016X;
London, Stephanie/0000-0003-4911-5290; Wu, Michael
C./0000-0002-3357-6570; Ruiz Arenas, Carlos/0000-0002-6014-3498; Kumar,
Ashish/0000-0002-7075-5930; Sharp, Gemma/0000-0003-2906-4035; Gruzieva,
Olena/0000-0003-4147-5654; xu, zongli/0000-0002-9034-8902; BAIZ,
Nour/0000-0001-6165-3935; Wilcox, Allen/0000-0002-3376-1311; taylor,
jack/0000-0001-5303-6398; Salas, Lucas A/0000-0002-2279-4097; Kull,
Inger/0000-0001-6096-3771; Pinart, Mariona/0000-0002-8223-1325; Anto,
J/0000-0002-4736-8529; Holloway, John/0000-0001-9998-0464; Gaunt,
Tom/0000-0003-0924-3247; Heude, Barbara/0000-0002-1565-1629; Kere,
Juha/0000-0003-1974-0271; Sunyer, J/0000-0002-2602-4110; Davey Smith,
George/0000-0002-1407-8314; GHANTOUS, Akram/0000-0002-2582-6402;
Vrijheid, M/0000-0002-7090-1758
FU Medical Research Council [MC_PC_15018, MC_UU_12013/1, MC_UU_12013/2,
MC_UU_12013/8]; NIDDK NIH HHS [R01 DK085173]; NIEHS NIH HHS [P30
ES007048, R01 ES016772, R21 ES014947]; Wellcome Trust [102215]
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 7
PY 2016
VL 98
IS 4
BP 680
EP 696
DI 10.1016/j.ajhg.2016.02.019
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ4UO
UT WOS:000374203800007
PM 27040690
ER
PT J
AU Qin, HD
Liao, XY
Chen, YB
Huang, SY
Xue, WQ
Li, FF
Ge, XS
Liu, DQ
Cai, QY
Long, JR
Li, XZ
Hu, YZ
Zhang, SD
Zhang, LJ
Lehrman, B
Scott, AF
Lin, DX
Zeng, YX
Shugart, YY
Jia, WH
AF Qin, Hai-De
Liao, Xiao-Yu
Chen, Yuan-Bin
Huang, Shao-Yi
Xue, Wen-Qiong
Li, Fang-Fang
Ge, Xiao-Song
Liu, De-Qing
Cai, Qiuyin
Long, Jirong
Li, Xi-Zhao
Hu, Ye-Zhu
Zhang, Shao-Dan
Zhang, Lan-Jun
Lehrman, Benjamin
Scott, Alan F.
Lin, Dongxin
Zeng, Yi-Xin
Shugart, Yin Yao
Jia, Wei-Hua
TI Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals
Critical Genes Underlying Tumorigenesis and Poor Prognosis
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID HUMAN HEPATOCELLULAR-CARCINOMA; COPY-NUMBER ALTERATION; WIDE
ASSOCIATION; CANCER-CELLS; FUNCTIONAL ANNOTATION; SUSCEPTIBILITY LOCI;
TUMOR PROGRESSION; MICRORNA TARGETS; SEQUENCING DATA; KITENIN
AB The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.
C1 [Qin, Hai-De; Liao, Xiao-Yu; Chen, Yuan-Bin; Huang, Shao-Yi; Xue, Wen-Qiong; Li, Fang-Fang; Ge, Xiao-Song; Liu, De-Qing; Li, Xi-Zhao; Hu, Ye-Zhu; Zhang, Shao-Dan; Zhang, Lan-Jun; Zeng, Yi-Xin; Jia, Wei-Hua] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
[Qin, Hai-De; Lehrman, Benjamin; Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Ge, Xiao-Song] Jiangnan Univ, Affiliated Hosp, Wuxi 214062, Peoples R China.
[Cai, Qiuyin; Long, Jirong] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Ingram Canc Ctr, Nashville, TN 37240 USA.
[Cai, Qiuyin; Long, Jirong] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37240 USA.
[Scott, Alan F.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
[Lin, Dongxin] Chinese Acad Med Sci, State Key Lab Mol Oncol, Beijing 100021, Peoples R China.
[Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
RP Jia, WH (reprint author), Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.; Shugart, YY (reprint author), NIMH, Unit Stat Genom, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
EM kay1yao@mail.nih.gov; jiawh@sysucc.org.cn
FU National Science Fund for Distinguished Young Scholars of China
[81325018]; Key Project for International Cooperation and Exchange of
the National Natural Science Foundation of China [81220108022]; National
Basic Research Program of China (973 program) [2011CB504303]; Intramural
Research Program, National Institute of Mental Health (NIMH), NIH
(IRP-NIMH-NIH) [MH002930-05]
FX We'd like to thank Profs. Xiao-ou Shu and Wei Zheng of the
Vanderbilt-Ingram Cancer Center for their kind advice in the course of
sample preparation, exon capture, and deep sequencing. We thank Prof.
Song Gao for his kind help in protein structure prediction. We also
thank Bank of Tumor Resources, Cancer Center Sun Yat-sen University for
providing the ESCC samples in this study. This work was supported by the
grants from the National Science Fund for Distinguished Young Scholars
of China (grant no. 81325018), the Key Project for International
Cooperation and Exchange of the National Natural Science Foundation of
China (grant no. 81220108022), the National Basic Research Program of
China (973 program no. 2011CB504303). The authors gratefully acknowledge
the support of the Intramural Research Program, National Institute of
Mental Health (NIMH), NIH (IRP-NIMH-NIH, grant no. MH002930-05). The
views expressed in this presentation do not necessarily represent the
views of the the NIMH, the NIH, the US Department of Health and Human
Services, or the United States Government.
NR 59
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 7
PY 2016
VL 98
IS 4
BP 709
EP 727
DI 10.1016/j.ajhg.2016.02.021
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ4UO
UT WOS:000374203800009
PM 27058444
ER
PT J
AU Leslie, EJ
Liu, H
Carlson, JC
Shaffer, JR
Feingold, E
Wehby, G
Laurie, CA
Jain, D
Laurie, CC
Doheny, KF
McHenry, T
Resick, J
Sanchez, C
Jacobs, J
Emanuele, B
Vieira, AR
Neiswanger, K
Standley, J
Czeize, AE
Deleyiannis, F
Christensen, K
Munger, RG
Lie, RT
Wilcox, A
Romitti, PA
Field, LL
Padilla, CD
Cutiongco-de la Paz, EMC
Lidral, AC
Valencia-Ramirez, LC
Lopez-Palacio, AM
Valencia, DR
Arcos-Burgos, M
Castilla, EE
Mereb, JC
Poletta, FA
Orioli, IM
Carvalho, FM
Hecht, JT
Blanton, SH
Buxo, CJ
Butali, A
Mossey, PA
Adeyemo, WL
James, O
Braimah, RO
Aregbesola, BS
Eshete, MA
Deribew, M
Koruyucu, M
Seymen, F
Ma, L
de Salamanca, JE
Weinberg, SM
Moreno, L
Cornell, RA
Murray, JC
Marazita, ML
AF Leslie, Elizabeth J.
Liu, Huan
Carlson, Jenna C.
Shaffer, John R.
Feingold, Eleanor
Wehby, George
Laurie, Cecelia A.
Jain, Deepti
Laurie, Cathy C.
Doheny, Kimberly F.
McHenry, Toby
Resick, Judith
Sanchez, Carla
Jacobs, Jennifer
Emanuele, Beth
Vieira, Alexandre R.
Neiswanger, Katherine
Standley, Jennifer
Czeize, Andrew E.
Deleyiannis, Frederic
Christensen, Kaare
Munger, Ronald G.
Lie, Rolv T.
Wilcox, Allen
Romitti, Paul A.
Field, L. Leigh
Padilla, Carmencita D.
Cutiongco-de la Paz, Eva Maria C.
Lidral, Andrew C.
Valencia-Ramirez, Luz Consuelo
Lopez-Palacio, Ana Maria
Valencia, Dora Rivera
Arcos-Burgos, Mauricio
Castilla, Eduardo E.
Mereb, Juan C.
Poletta, Fernando A.
Orioli, Ieda M.
Carvalho, Flavia M.
Hecht, Jacqueline T.
Blanton, Susan H.
Buxo, Carmen J.
Butali, Azeez
Mossey, Peter A.
Adeyemo, Wasiu L.
James, Olutayo
Braimah, Ramat O.
Aregbesola, Babatunde S.
Eshete, Mekonen A.
Deribew, Milliard
Koruyucu, Mine
Seymen, Figen
Ma, Lian
de Salamanca, Javier Enriquez
Weinberg, Seth M.
Moreno, Lina
Cornell, Robert A.
Murray, Jeffrey C.
Marazita, Mary L.
TI A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies
an Etiologic Missense Variant in GRHL3
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CAUSE VAN; LIP; RISK; LINKAGE; LOCI; MUTATIONS; DEFECTS; COHORT; GENES;
WOUDE
AB Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 x 10(-9)) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.
C1 [Leslie, Elizabeth J.; Carlson, Jenna C.; Shaffer, John R.; Feingold, Eleanor; McHenry, Toby; Resick, Judith; Sanchez, Carla; Jacobs, Jennifer; Emanuele, Beth; Vieira, Alexandre R.; Neiswanger, Katherine; Weinberg, Seth M.; Marazita, Mary L.] Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Sch Dent Med, Pittsburgh, PA 15219 USA.
[Liu, Huan; Cornell, Robert A.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
[Liu, Huan] Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hu, Sch & Hosp Stomatol, Wuhan 430079, Peoples R China.
[Liu, Huan] Wuhan Univ, Key Lab Oral Biomed, Minist Educ, Sch & Hosp Stomatol, Wuhan 430079, Peoples R China.
[Carlson, Jenna C.; Feingold, Eleanor] Univ Pittsburgh, Depat Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Shaffer, John R.; Feingold, Eleanor; Vieira, Alexandre R.; Marazita, Mary L.] Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Wehby, George] Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, Iowa City, IA 52246 USA.
[Laurie, Cecelia A.; Jain, Deepti; Laurie, Cathy C.] Univ Washington, Dept Biostat, Genet Coordinating Ctr, Seattle, WA 98195 USA.
[Doheny, Kimberly F.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA.
[Standley, Jennifer; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Czeize, Andrew E.] Fdn Community Control Hereditary Dis, H-1051 Budapest, Hungary.
[Deleyiannis, Frederic] Univ Colorado, Sch Med, Dept Surg Plast & Reconstruct Surg, Denver, CO 80045 USA.
[Christensen, Kaare] Univ Southern Denmark, Dept Epidemiol, Inst Publ Hlth, DK-5230 Odense, Denmark.
[Munger, Ronald G.] Utah State Univ, Dept Nutr Dietet & Food Sci, Logan, UT 84322 USA.
[Lie, Rolv T.] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway.
[Wilcox, Allen] NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
[Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA 52246 USA.
[Field, L. Leigh] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
[Padilla, Carmencita D.; Cutiongco-de la Paz, Eva Maria C.] Univ Philippines Manila, Inst Human Genet, Natl Inst Hlth, Manila 1000, Philippines.
[Cutiongco-de la Paz, Eva Maria C.] Univ Philippines Manila, Dept Pediat, Coll Med, Manila 1000, Philippines.
[Cutiongco-de la Paz, Eva Maria C.] Univ Philippines, Philippine Genome Ctr, Manila 1101, Philippines.
[Lidral, Andrew C.; Moreno, Lina] Univ Iowa, Dept Orthodont, Coll Dent, Iowa City, IA 52242 USA.
[Valencia-Ramirez, Luz Consuelo] Fdn Unica Noel, Medellin 050012, Colombia.
[Lopez-Palacio, Ana Maria] Univ Antioquia, Dept Basic Integrated Studies, Coll Dent, Medellin 050001, Colombia.
[Valencia, Dora Rivera] Univ Antioquia, Populat Genet & Mutacarcinogenesis Grp, Medellin 050001, Colombia.
[Arcos-Burgos, Mauricio] Australian Natl Univ, Genom & Predict Med, Genome Biol Dept, John Curtin Sch Med Res,ANU Coll Med Biol & Envir, Canberra, ACT 0200, Australia.
[Castilla, Eduardo E.; Poletta, Fernando A.; Carvalho, Flavia M.] CEMIC Ctr Med Educ & Clin Res, RA-1431 Buenos Aires, DF, Argentina.
[Castilla, Eduardo E.; Poletta, Fernando A.; Carvalho, Flavia M.] Fiocruz MS, Lab Congenital Malformat Epidemiol, Inst Oswaldo Cruz, BR-21040360 Rio De Janeiro, Brazil.
[Castilla, Eduardo E.; Poletta, Fernando A.; Orioli, Ieda M.] INAGEMP Natl Inst Populat Med Genet, ECLAMC Latin Amer Collaborat Study Congenital Mal, BR-21941617 Rio De Janeiro, Brazil.
[Mereb, Juan C.] Hosp Area, ECLAMC Latin Amer Collaborat Study Congenital Mal, RA-8430 El Bolson, Argentina.
[Orioli, Ieda M.] Univ Fed Rio de Janeiro, Dept Genet, Inst Biol, BR-21941617 Rio De Janeiro, Brazil.
[Hecht, Jacqueline T.] Univ Texas Houston, Hlth Sci Ctr, Dept Pediat, Houston, TX 77030 USA.
[Blanton, Susan H.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Hussman Inst Human Gen,Mailman Sch Med, Miami, FL 33124 USA.
[Buxo, Carmen J.] Univ Puerto Rico, Sch Dent Med, San Juan, PR 00936 USA.
[Butali, Azeez] Univ Iowa, Dept Oral Pathol Radiol & Med, Dows Inst Dent Res, Coll Dent, Iowa City, IA 52242 USA.
[Mossey, Peter A.] Univ Dundee, Dept Orthodont, Dundee DD1 4HN, Scotland.
[Adeyemo, Wasiu L.; James, Olutayo] Univ Lagos, Dept Oral & Maxillofacial Surg, Coll Med, PMB 12003, Lagos, Nigeria.
[Braimah, Ramat O.; Aregbesola, Babatunde S.] Obafemi Awolowo Univ Ile Ife, Dept Oral & Maxillofacial Surg, PMB 13, Ife, Nigeria.
[Eshete, Mekonen A.; Deribew, Milliard] Univ Addis Ababa, Dept Surg, Sch Med, POB 26493, Addis Ababa, Ethiopia.
[Koruyucu, Mine; Seymen, Figen] Istanbul Univ, Dept Pedodont, TR-34116 Istanbul, Turkey.
[Ma, Lian] Peking Univ, Sch Stomatol, Beijing 100081, Peoples R China.
[de Salamanca, Javier Enriquez] Univ Nino Jesus, Hosp Infantil, Unidad Cirugia Plast, Madrid 28009, Spain.
[Marazita, Mary L.] Univ Pittsburgh, Sch Med, Clin & Translat Sci, Pittsburgh, PA 15213 USA.
RP Marazita, ML (reprint author), Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Sch Dent Med, Pittsburgh, PA 15219 USA.; Marazita, ML (reprint author), Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.; Marazita, ML (reprint author), Univ Pittsburgh, Sch Med, Clin & Translat Sci, Pittsburgh, PA 15213 USA.
EM marazita@pitt.edu
RI Christensen, Kaare/C-2360-2009;
OI Christensen, Kaare/0000-0002-5429-5292; Wilcox,
Allen/0000-0002-3376-1311
FU NIH [X01-HG007845, R01-DE016148, HHSN268201200008I, R01-DE020895,
U01-DE018993]
FX We dedicate this paper to the memory of our colleagues Dr. Andrew
Czeizel and Dr. Juan C. Mereb; they will be missed. Many thanks to the
participating families who made the studies summarized here possible and
who provided on-going inspiration to the investigators. The tireless
effort by the dedicated field staff and collaborators was similarly
essential to the success of this study. This work was supported by
grants from the NIH including X01-HG007845 and R01-DE016148 (to M.L.M.),
and genotyping and data cleaning were provided via an NIH contract to
the Johns Hopkins Center for Inherited Disease Research
(HHSN268201200008I). The replication studies were funded by NIH grants
R01-DE020895 (to G.L.W.) and U01-DE018993 to Dr. Tern Beaty at Johns
Hopkins University School of Public Health. See the Supplemental
Acknowledgments for additional grant support and full acknowledgments.
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD APR 7
PY 2016
VL 98
IS 4
BP 744
EP 754
DI 10.1016/j.ajhg.2016.02.014
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ4UO
UT WOS:000374203800012
PM 27018472
ER
PT J
AU Baranello, L
Wojtowicz, D
Cui, KR
Devaiah, BN
Chung, HJ
Chan-Salis, KY
Guha, R
Wilson, K
Zhang, XH
Zhang, HL
Piotrowski, J
Thomas, CJ
Singer, DS
Pugh, BF
Pommier, Y
Przytycka, TM
Kouzine, F
Lewis, BA
Zhao, KJ
Levens, D
AF Baranello, Laura
Wojtowicz, Damian
Cui, Kairong
Devaiah, Ballachanda N.
Chung, Hye-Jung
Chan-Salis, Ka Yim
Guha, Rajarshi
Wilson, Kelli
Zhang, Xiaohu
Zhang, Hongliang
Piotrowski, Jason
Thomas, Craig J.
Singer, Dinah S.
Pugh, B. Franklin
Pommier, Yves
Przytycka, Teresa M.
Kouzine, Fedor
Lewis, Brian A.
Zhao, Keji
Levens, David
TI RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient
Transcription
SO CELL
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; CARBOXY-TERMINAL DOMAIN; P-TEFB; IN-VIVO;
DEPENDENT TRANSCRIPTION; SELECTIVE-INHIBITION; CLEAVAGE COMPLEXES; PAUSE
RELEASE; GENOME-WIDE; CTD CODE
AB We report a mechanism through which the transcription machinery directly controls topoisomerase 1 (TOP1) activity to adjust DNA topology throughout the transcription cycle. By comparing TOP1 occupancy using chromatin immunoprecipitation sequencing (ChIP-seq) versus TOP1 activity using topoisomerase 1 sequencing (TOP1-seq), a method reported here to map catalytically engaged TOP1, TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. TOP1 stimulation is strongly dependent on the kinase activity of BRD4, a protein that phosphorylates Ser2-CTD and regulates RNAPII pause-release. Thus the coordinated action of BRD4 and TOP1 overcame the torsional stress opposing transcription as RNAPII commenced elongation but preserved negative supercoiling that assists promotermelting at start sites. This nexus between transcription and DNA topology promises to elicit new strategies to intercept pathological gene expression.
C1 [Baranello, Laura; Chung, Hye-Jung; Kouzine, Fedor; Levens, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wojtowicz, Damian; Przytycka, Teresa M.] NCBI, Computat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Devaiah, Ballachanda N.; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Chan-Salis, Ka Yim; Pugh, B. Franklin] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Guha, Rajarshi; Wilson, Kelli; Zhang, Xiaohu; Thomas, Craig J.] NCATS, Div Preclin Innovat, NIH, Rockville, MD 20850 USA.
[Zhang, Hongliang; Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Hongliang; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Piotrowski, Jason; Lewis, Brian A.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
RP Levens, D (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.; Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov; levens@helix.nih.gov
FU Intramural Research Program of the US NIH; Center for Cancer Research of
the National Cancer Institute; National Heart, Lung and Blood Institute;
National Library of Medicine
FX Our research is supported by the Intramural Research Program of the US
NIH, Center for Cancer Research of the National Cancer Institute, the
National Heart, Lung and Blood Institute, and the National Library of
Medicine. The ChIP-seq and RNA-seq libraries were sequenced by the NHLBI
DNA Sequencing and Genomics Core Facility.
NR 74
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Z9 12
U1 10
U2 29
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 7
PY 2016
VL 165
IS 2
BP 357
EP 371
DI 10.1016/j.cell.2016.02.036
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3RJ
UT WOS:000374123000014
PM 27058666
ER
PT J
AU Bonsignori, M
Zhou, TQ
Sheng, ZZ
Chen, L
Gao, F
Joyce, MG
Ozorowski, G
Chuang, GY
Schramm, CA
Wiehe, K
Alam, SM
Bradley, T
Gladden, MA
Hwang, KK
Iyengar, S
Kumar, A
Lu, XZ
Luo, K
Mangiapani, MC
Parks, RJ
Song, HS
Acharya, P
Bailer, RT
Cao, A
Druz, A
Georgiev, IS
Kwon, YD
Louder, MK
Zhang, BS
Zheng, AQ
Hill, BJ
Kong, R
Soto, C
Mullikin, JC
Douek, DC
Montefiori, DC
Moody, MA
Shaw, GM
Hahn, BH
Kelsoe, G
Hraber, PT
Korber, BT
Boyd, SD
Fire, AZ
Kepler, TB
Shapiro, L
Ward, AB
Mascola, JR
Liao, HX
Kwong, PD
Haynes, BF
AF Bonsignori, Mattia
Zhou, Tongqing
Sheng, Zizhang
Chen, Lei
Gao, Feng
Joyce, M. Gordon
Ozorowski, Gabriel
Chuang, Gwo-Yu
Schramm, Chaim A.
Wiehe, Kevin
Alam, S. Munir
Bradley, Todd
Gladden, Morgan A.
Hwang, Kwan-Ki
Iyengar, Sheelah
Kumar, Amit
Lu, Xiaozhi
Luo, Kan
Mangiapani, Michael C.
Parks, Robert J.
Song, Hongshuo
Acharya, Priyamvada
Bailer, Robert T.
Cao, Allen
Druz, Aliaksandr
Georgiev, Ivelin S.
Kwon, Young D.
Louder, Mark K.
Zhang, Baoshan
Zheng, Anqi
Hill, Brenna J.
Kong, Rui
Soto, Cinque
Mullikin, James C.
Douek, Daniel C.
Montefiori, David C.
Moody, Michael A.
Shaw, George M.
Hahn, Beatrice H.
Kelsoe, Garnett
Hraber, Peter T.
Korber, Bette T.
Boyd, Scott D.
Fire, Andrew Z.
Kepler, Thomas B.
Shapiro, Lawrence
Ward, Andrew B.
Mascola, John R.
Liao, Hua-Xin
Kwong, Peter D.
Haynes, Barton F.
CA NISC Comparative Sequencing Progra
TI Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a
CD4-Mimic Antibody
SO CELL
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; B-CELL RECEPTORS; VACCINE DEVELOPMENT;
IMMUNOGEN DESIGN; FOUNDER VIRUS; AUTOREACTIVITY; INFECTION; INDUCTION;
MEMBRANE; BINDING
AB Antibodies with ontogenies from V(H)1-2 or V(H)1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a V(H)1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the V(H)1-46 gene, which closely resembled V(H)1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.
C1 [Bonsignori, Mattia; Gao, Feng; Wiehe, Kevin; Alam, S. Munir; Bradley, Todd; Gladden, Morgan A.; Hwang, Kwan-Ki; Iyengar, Sheelah; Kumar, Amit; Lu, Xiaozhi; Luo, Kan; Mangiapani, Michael C.; Parks, Robert J.; Song, Hongshuo; Montefiori, David C.; Moody, Michael A.; Kelsoe, Garnett; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Bonsignori, Mattia; Gao, Feng; Wiehe, Kevin; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA.
[Zhou, Tongqing; Chen, Lei; Joyce, M. Gordon; Chuang, Gwo-Yu; Acharya, Priyamvada; Bailer, Robert T.; Cao, Allen; Druz, Aliaksandr; Georgiev, Ivelin S.; Kwon, Young D.; Louder, Mark K.; Zhang, Baoshan; Zheng, Anqi; Hill, Brenna J.; Kong, Rui; Soto, Cinque; Douek, Daniel C.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sheng, Zizhang; Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Sheng, Zizhang; Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA.
[Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, CAVD, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Georgiev, Ivelin S.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Georgiev, Ivelin S.] Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37232 USA.
[Georgiev, Ivelin S.] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA.
[Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Montefiori, David C.] Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA.
[Montefiori, David C.; Moody, Michael A.] Duke Univ, Sch Med, Dept Pediat, Durham, NC 27710 USA.
[Montefiori, David C.; Moody, Michael A.; Kelsoe, Garnett; Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Hraber, Peter T.; Korber, Bette T.] Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87544 USA.
[Boyd, Scott D.; Fire, Andrew Z.] Stanford Sch Med, Dept Pathol, Palo Alto, CA 94305 USA.
[Kepler, Thomas B.] Boston Univ, Dept Microbiol, Boston, MA 02118 USA.
[Kepler, Thomas B.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Duke Global Hlth Inst, Durham, NC 27710 USA.
RP Haynes, BF (reprint author), Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.; Haynes, BF (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA.; Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.; Haynes, BF (reprint author), Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA.; Haynes, BF (reprint author), Duke Univ, Sch Med, Duke Global Hlth Inst, Durham, NC 27710 USA.
EM pdkwong@nih.gov; barton.haynes@duke.edu
RI Ward, Andrew/F-9203-2014; Zhou, Tongqing/A-6880-2010; Kwon, Young
Do/A-6957-2010;
OI Ward, Andrew/0000-0001-7153-3769; Zhou, Tongqing/0000-0002-3935-4637;
Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897
FU Division of AIDS, NIAID, NIH Center for HIV/AIDS Vaccine
Immunology-Immunogen Discovery [UM1 AI100645]; Scripps CHAVI-ID [UM1
AI100663]; International AIDS Vaccine Initiative; Bill and Melinda Gates
Foundation; Intramural Research Program of the Vaccine Research Center,
NIAID, NIH; NIH [P01-AI104722]; US Department of Energy, Basic Energy
Sciences, Office of Science [W-31-109-Eng-38]
FX The authors thank K. Lloyd, A. Eaton, T. Von Holle, T. Gurley, L.
Armand, D. Kozink, A. Cooper, F. Perrin, J. Pritchett, A. Foulger, G.
Hernandez, S. Arora, R. Kauffman, A. Trama of the Duke Human Vaccine
Institute, J. Whitesides, D. Marshall and the DHVI Flow Cytometry Core
for technical assistance, and K. Soderberg for project coordination;
members of the Structural Biology Section and Structural Bioinformatics
Core, Vaccine Research Center, for discussions and comments on the
manuscript; J. Baalwa, D. Ellenberger, K. Hong, J. Kim, F. McCutchan, L.
Morris, J. Overbaugh, E. Sanders-Buell, R. Swanstrom, M. Thomson, S.
Tovanabutra, C. Williamson, and L. Zhang for contributing HIV-1 Envelope
plasmids. The authors also thank Gift Kamanga, Michael S. Cohen, and the
CHAVI clinical team for clinical trial participant recruitment and
sample provision. Supported by a grant from the Division of AIDS, NIAID,
NIH Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery UM1
AI100645 (Duke CHAVI-ID), the Scripps CHAVI-ID (UM1 AI100663), the
International AIDS Vaccine Initiative, and the Bill and Melinda Gates
Foundation (CAVD) to A.B.W. Support for this work was provided by the
Intramural Research Program of the Vaccine Research Center, NIAID, NIH,
and by NIH grant P01-AI104722. Use of sector 22 (Southeast Region
Collaborative Access team) at the Advanced Photon Source was supported
by the US Department of Energy, Basic Energy Sciences, Office of Science
(contract W-31-109-Eng-38). M.B., P.T.H., B.T.K., H.-X.L. and B.F.H.
have filed patent applications directed to antibodies and use of various
envelopes as immunogens. None of the authors declared conflicts of
interest.
NR 44
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U1 4
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 7
PY 2016
VL 165
IS 2
BP 449
EP 463
DI 10.1016/j.cell.2016.02.022
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3RJ
UT WOS:000374123000022
PM 26949186
ER
PT J
AU Goncalves, BP
Prevots, DR
Kabyemela, E
Fried, M
Duffy, PE
AF Goncalves, Bronner P.
Prevots, D. Rebecca
Kabyemela, Edward
Fried, Michal
Duffy, Patrick E.
TI Preparing for future efficacy trials of severe malaria vaccines
SO VACCINE
LA English
DT Article
DE Severe malaria; Vaccine; Clinical trial; Immunity; Sample size
ID PLASMODIUM-FALCIPARUM MALARIA; TRANSMISSION; CHILDREN; AFRICA; MORBIDITY
AB Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks. Published by Elsevier Ltd.
C1 [Goncalves, Bronner P.; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Goncalves, Bronner P.; Prevots, D. Rebecca] NIAID, Lab Clin Infect Dis, Epidemiol Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kabyemela, Edward; Fried, Michal; Duffy, Patrick E.] Ctr Infect Dis Res, MOMS Project, Seattle, WA USA.
[Kabyemela, Edward; Fried, Michal; Duffy, Patrick E.] Muheza Designated Dist Hosp, Muheza, Tanzania.
RP Duffy, PE (reprint author), NIAID, NIH, Lab Malaria Immunol & Vaccinol, Twinbrook 1,Rm 1111,5640 Fishers Ln, Rockville, MD 20852 USA.
EM Patrick.duffy@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH [R01AI52059];
Bill & Melinda Gates Foundation [29202]; Foundation for the National
Institutes of Health through the Grand Challenges in Global Health
Initiative [1364]; US National Institutes of Health Fogarty
International Center (FIC) [D43 TW005509]
FX This work was supported by the Division of Intramural Research (DIR) and
the extramural program [grant R01AI52059] of the National Institute of
Allergy and Infectious Diseases, NIH; the Bill & Melinda Gates
Foundation [grant 29202]; the Foundation for the National Institutes of
Health through the Grand Challenges in Global Health Initiative [grant
1364]; the US National Institutes of Health Fogarty International Center
(FIC) [grant D43 TW005509]. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 14
TC 1
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U1 1
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD APR 7
PY 2016
VL 34
IS 16
BP 1865
EP 1867
DI 10.1016/j.vaccine.2016.02.053
PG 3
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DJ4SO
UT WOS:000374198500002
PM 26923455
ER
PT J
AU Kumar, S
Rajagopalan, S
Sarkar, P
Dorward, DW
Peterson, ME
Liao, HS
Guillermier, C
Steinhauser, ML
Vogel, SS
Long, EO
AF Kumar, Santosh
Rajagopalan, Sumati
Sarkar, Pabak
Dorward, David W.
Peterson, Mary E.
Liao, Hsien-Shun
Guillermier, Christelle
Steinhauser, Matthew L.
Vogel, Steven S.
Long, Eric O.
TI Zinc-Induced Polymerization of Killer-Cell Ig-like Receptor into
Filaments Promotes Its Inhibitory Function at Cytotoxic Immunological
Synapses
SO MOLECULAR CELL
LA English
DT Article
ID NK CELLS; SELF-ASSOCIATION; ACTIVATION; INNATE; PROTEIN; RECRUITMENT;
MECHANISM; PARADIGM; IMMUNITY; DISEASE
AB The inhibitory function of killer cell immunoglobulin-like receptors (KIR) that bind HLA-C and block activation of human natural killer (NK) cells is dependent on zinc. We report that zinc induced the assembly of soluble KIR into filamentous polymers, as detected by electron microscopy, which depolymerized after zinc chelation. Similar KIR filaments were isolated from lysates of cells treated with zinc, and membrane protrusions enriched in zinc were detected on whole cells by scanning electron microscopy and imaging mass spectrometry. Two independent mutations in the extracellular domain of KIR, away from the HLA-C binding site, impaired zinc-driven polymerization and inhibitory function. KIR filaments formed spontaneously, without the addition of zinc, at functional inhibitory immunological synapses of NK cells with HLA-C+ cells. Adding to the recent paradigm of signal transduction through higher order molecular assemblies, zinc-induced polymerization of inhibitory KIR represents an unusual mode of signaling by a receptor at the cell surface.
C1 [Kumar, Santosh; Rajagopalan, Sumati; Peterson, Mary E.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Sarkar, Pabak; Vogel, Steven S.] NIAAA, Lab Mol Physiol, NIH, Rockville, MD 20852 USA.
[Dorward, David W.] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Liao, Hsien-Shun] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Guillermier, Christelle; Steinhauser, Matthew L.] Brigham & Womens Hosp, Ctr NanoImaging, Cambridge, MA 02138 USA.
[Guillermier, Christelle; Steinhauser, Matthew L.] Brigham & Womens Hosp, Div Genet, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Guillermier, Christelle; Steinhauser, Matthew L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Liao, Hsien-Shun] Natl Taiwan Univ, Dept Mech Engn, Taipei 10617, Taiwan.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM elong@nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institute on Alcohol Abuse and Alcoholism; National Institute of
Biomedical Imaging and Bioengineering; NIH [K08DK090147, RO3DK106477]
FX We thank David Narum and Karine Reiter for assistance with circular
dichroism and Shailesh Kumar for amyloid fibrils of Ure-2. HLA-C*0401
tetramer was made at the NIH Tetramer Core Facility. This work was
supported by the Intramural Research Programs at the National Institute
of Allergy and Infectious Diseases (to E.O.L.), National Institute on
Alcohol Abuse and Alcoholism (to S.S.V.), and National Institute of
Biomedical Imaging and Bioengineering (to H.-S.L.), NIH, and by NIH
grants K08DK090147 and RO3DK106477 (to M.L.S.).
NR 43
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U1 3
U2 4
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD APR 7
PY 2016
VL 62
IS 1
BP 21
EP 33
DI 10.1016/j.molcel.2016.03.009
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DJ3QB
UT WOS:000374119600005
PM 27058785
ER
PT J
AU Roma, EH
Macedo, JP
Goes, GR
Goncalves, JL
de Castro, W
Cisalpino, D
Vieira, LQ
AF Roma, Eric Henrique
Macedo, Juan Pereira
Goes, Grazielle Ribeiro
Goncalves, Juliana Lauar
de Castro, Waldione
Cisalpino, Daniel
Vieira, Leda Quercia
TI Impact of reactive oxygen species (ROS) on the control of parasite loads
and inflammation in Leishmania amazonensis infection
SO PARASITES & VECTORS
LA English
DT Article
DE Leishmania amazonensis; ROS; NOX2; Neutrophils; Inflammation
ID CHRONIC GRANULOMATOUS-DISEASE; PHAGOCYTE NADPH OXIDASE; MURINE CUTANEOUS
LEISHMANIASIS; DEPENDENT KILLING MECHANISM; NECROSIS-FACTOR-ALPHA;
CD4(+) T-CELLS; NITRIC-OXIDE; IN-VIVO; NEUTROPHIL APOPTOSIS;
INTERFERON-GAMMA
AB Background: Reactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms. ROS have different effects on parasites of the genus Leishmania: some parasites are susceptible to their action, while others seem to be resistant. The role of ROS in L. amazonensis infection in vivo has not been addressed to date.
Methods: In this study, C57BL/6 wild-type mice (WT) and mice genetically deficient in ROS production by phagocytes (gp91(phox-/-)) were infected with metacyclic promastigotes of L. amazonensis to address the effect of ROS in parasite control. Inflammatory cytokines, parasite loads and myeloperoxidase (MPO) activity were evaluated. In parallel, in vitro infection of peritoneal macrophages was assessed to determine parasite killing, cytokine, NO and ROS production.
Results: In vitro results show induction of ROS production by infected peritoneal macrophages, but no effect in parasite killing. Also, ROS do not seem to be important to parasite killing in vivo, but they control lesion sizes at early stages of infection. IFN-gamma, TNF-alpha and IL-10 production did not differ among mouse strains. Myeloperoxidase assay showed augmented neutrophils influx 6 h and 72 h post-infection in gp91(phox-/-) mice, indicating a larger inflammatory response in gp91(phox-/-) even at early time points. At later time points, neutrophil numbers in lesions correlated with lesion size: larger lesions in gp91(phox-/-) at earlier times of infection corresponded to larger neutrophil infiltrates, while larger lesions in WT mice at the later points of infection also displayed larger numbers of neutrophils.
Conclusion: ROS do not seem to be important in L. amazonensis killing, but they regulate the inflammatory response probably by controlling neutrophils numbers in lesions.
C1 [Roma, Eric Henrique; Macedo, Juan Pereira; Goes, Grazielle Ribeiro; Goncalves, Juliana Lauar; de Castro, Waldione; Vieira, Leda Quercia] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil.
[Cisalpino, Daniel] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, Brazil.
[Roma, Eric Henrique; Goncalves, Juliana Lauar] Fiocruz MS, Inst Nacl Infectol, BR-21045900 Rio De Janeiro, RJ, Brazil.
[de Castro, Waldione] NIAID, Lab Malaria & Vector Res, Vector Mol Biol Sect, NIH, Rockville, MD USA.
RP Vieira, LQ (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil.
EM lqvieira@icb.ufmg.br
RI Macedo, Juan/B-4151-2017;
OI Macedo, Juan/0000-0001-5759-1196; Roma, Eric /0000-0001-5265-5277
FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
[CDS-RED-00013-14, APQ-02308-13, APQ-01419-14]
FX EHR, GRG, JLG, DC and LQV are CNPq fellows. JPM was a CAPES fellow. This
work was supported by grants from Fundacao de Amparo a Pesquisa do
Estado de Minas Gerais (FAPEMIG, CDS-RED-00013-14, APQ-02308-13 and
APQ-01419-14). The authors are members of the INCT de Processos Redox em
Biomedicina-Redoxoma (FAPESP/CNPq/CAPES, proc 573530/2008-4). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 76
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Z9 2
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD APR 7
PY 2016
VL 9
AR 193
DI 10.1186/s13071-016-1472-y
PG 13
WC Parasitology
SC Parasitology
GA DJ3WB
UT WOS:000374136300001
PM 27056545
ER
PT J
AU Kobayashi, W
Takaku, M
Machida, S
Tachiwana, H
Maehara, K
Ohkawa, Y
Kurumizaka, H
AF Kobayashi, Wataru
Takaku, Motoki
Machida, Shinichi
Tachiwana, Hiroaki
Maehara, Kazumitsu
Ohkawa, Yasuyuki
Kurumizaka, Hitoshi
TI Chromatin architecture may dictate the target site for DMC1, but not for
RAD51, during homologous pairing
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DOUBLE-STRAND BREAK; MEIOTIC RECOMBINATION INITIATION; SYNAPTONEMAL
COMPLEX-FORMATION; ESCHERICHIA-COLI RECA; SACCHAROMYCES-CEREVISIAE;
CHROMOSOME SYNAPSIS; YEAST MEIOSIS; PHD FINGER; HOT-SPOT; DNA
AB In eukaryotes, genomic DNA is compacted as chromatin, in which histones and DNA form the nucleosome as the basic unit. DMC1 and RAD51 are essential eukaryotic recombinases that mediate homologous chromosome pairing during homologous recombination. However, the means by which these two recombinases distinctly function in chromatin have remained elusive. Here we found that, in chromatin, the human DMC1-single-stranded DNA complex bypasses binding to the nucleosome, and preferentially promotes homologous pairing at the nucleosome-depleted regions. Consistently, DMC1 forms ternary complex recombination intermediates with the nucleosome-free DNA or the nucleosome-depleted DNA region. Surprisingly, removal of the histone tails improperly enhances the nucleosome binding by DMC1. In contrast, RAD51 does not specifically target the nucleosome-depleted region in chromatin. These are the first demonstrations that the chromatin architecture specifies the sites to promote the homologous recombination reaction by DMC1, but not by RAD51.
C1 [Kobayashi, Wataru; Takaku, Motoki; Machida, Shinichi; Tachiwana, Hiroaki; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
[Maehara, Kazumitsu; Ohkawa, Yasuyuki] Kyushu Univ, Med Inst Bioregulat, Div Transcript, Fukuoka 8128582, Japan.
[Kurumizaka, Hitoshi] Waseda Univ, Inst Med Oriented Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
[Takaku, Motoki] NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kurumizaka, H (reprint author), Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.; Kurumizaka, H (reprint author), Waseda Univ, Inst Med Oriented Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM kurumizaka@waseda.jp
RI Ohkawa, Yasuyuki/C-4087-2016
OI Ohkawa, Yasuyuki/0000-0001-6440-9954
FU MEXT KAKENHI [25116002, 25131706]; JSPS KAKENHI [25250023, 26890023];
Platform for Drug Discovery, Informatics, and Structural Life Science
from MEXT, Japan; Waseda Research Institute for Science and Engineering;
Waseda University; Japan Society for the Promotion of Science for Young
Scientists
FX We thank Dr. Craig L. Peterson for providing the plasmid DNA containing
the tandem 5S DNA arrays. We also thank Mr. A. Esaki (Waseda University)
for his contribution in the initial stage of this project. This work was
supported in part by MEXT KAKENHI Grant Numbers 25116002 [to H.K.] and
25131706 [to Y.O.], JSPS KAKENHI Grant Numbers 25250023 [to H.K.] and
26890023 [to S.M.], and the Platform for Drug Discovery, Informatics,
and Structural Life Science from MEXT, Japan [to H.K.]. H.K. was also
supported by the Waseda Research Institute for Science and Engineering
and Waseda University. W.K. was supported by Research Fellowships of the
Japan Society for the Promotion of Science for Young Scientists.
NR 62
TC 0
Z9 0
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 7
PY 2016
VL 6
AR 24228
DI 10.1038/srep24228
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5ZZ
UT WOS:000373580300001
PM 27052786
ER
PT J
AU Collins, PY
Saxena, S
AF Collins, Pamela Y.
Saxena, Shekhar
TI Action on mental health needs global cooperation
SO NATURE
LA English
DT Editorial Material
ID DISORDERS; COUNTRIES
C1 [Collins, Pamela Y.] US Natl Inst Mental Hlth, Off Res Dispar & Global Mental Hlth, Bethesda, MD USA.
[Saxena, Shekhar] WHO, Dept Mental Hlth & Subst Abuse, CH-1211 Geneva, Switzerland.
RP Collins, PY (reprint author), US Natl Inst Mental Hlth, Off Res Dispar & Global Mental Hlth, Bethesda, MD USA.; Saxena, S (reprint author), WHO, Dept Mental Hlth & Subst Abuse, CH-1211 Geneva, Switzerland.
EM pamela.collins@nih.gov; saxenas@who.int
FU World Health Organization [001]
NR 7
TC 7
Z9 7
U1 4
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 25
EP 27
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500013
PM 27078549
ER
PT J
AU Gyamfi-Bannerman, C
Thom, EA
Blackwell, SC
Tita, ATN
Reddy, UM
Saade, GR
Rouse, DJ
McKenna, DS
Clark, EAS
Thorp, JM
Chien, EK
Peaceman, AM
Gibbs, RS
Swamy, GK
Norton, ME
Casey, BM
Caritis, SN
Tolosa, JE
Sorokin, Y
VanDorsten, JP
Jain, L
AF Gyamfi-Bannerman, C.
Thom, E. A.
Blackwell, S. C.
Tita, A. T. N.
Reddy, U. M.
Saade, G. R.
Rouse, D. J.
McKenna, D. S.
Clark, E. A. S.
Thorp, J. M., Jr.
Chien, E. K.
Peaceman, A. M.
Gibbs, R. S.
Swamy, G. K.
Norton, M. E.
Casey, B. M.
Caritis, S. N.
Tolosa, J. E.
Sorokin, Y.
VanDorsten, J. P.
Jain, L.
CA NICHD Maternal-Fetal Med Units Net
TI Antenatal Betamethasone for Women at Risk for Late Preterm Delivery
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID FETAL LUNG MATURATION; RESPIRATORY-DISTRESS; INFANTS; CORTICOSTEROIDS;
TRIAL; BIRTH; TERM; MORBIDITY; OUTCOMES
AB BACKGROUND
Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities.
METHODS
We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.
RESULTS
The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).
CONCLUSIONS
Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications.(Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.)
C1 [Gyamfi-Bannerman, C.] Columbia Univ, 622 W 168th St,PH-16, New York, NY 10032 USA.
[Thom, E. A.] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Blackwell, S. C.] 3niv Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA.
[Saade, G. R.] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Casey, B. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Tita, A. T. N.] Univ Alabama Birmingham, Birmingham, AL USA.
[Reddy, U. M.] Kennedy Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD USA.
[Rouse, D. J.] Brown Univ, Providence, RI 02912 USA.
[McKenna, D. S.] Ohio State Univ, Columbus, OH 43210 USA.
[Chien, E. K.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
[Clark, E. A. S.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Thorp, J. M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Swamy, G. K.] Duke Univ, Durham, NC USA.
[Peaceman, A. M.] Northwestern Univ, Chicago, IL USA.
[Gibbs, R. S.] Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO USA.
[Norton, M. E.] Stanford Univ, Stanford, CA 94305 USA.
[Caritis, S. N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Tolosa, J. E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Sorokin, Y.] Wayne State Univ, Detroit, MI USA.
[VanDorsten, J. P.] Med Univ S Carolina, Charleston, SC USA.
[Jain, L.] Emory Univ, Atlanta, GA 30322 USA.
RP Gyamfi-Bannerman, C (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, 622 W 168th St,PH-16, New York, NY 10032 USA.
EM cg2231@cumc.columbia.edu
FU NHLBI [HL098554, HL098354]; NICHD [HD21410, HD27915, HD27917, HD27869,
HD34116, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560,
HD53097, HD53118, HD68268, HD68258, HD68282, HD36801]; National Center
for Advancing Translational Sciences, National Institutes of Health [UL1
TR000040]
FX Supported by grants (HL098554 and HL098354) from the NHLBI, by grants
(HD21410, HD27915, HD27917, HD27869, HD34116, HD34208, HD40485, HD40500,
HD40512, HD40544, HD40545, HD40560, HD53097, HD53118, HD68268, HD68258,
HD68282, and HD36801) from the NICHD, and by a grant (UL1 TR000040) from
the National Center for Advancing Translational Sciences, National
Institutes of Health.
NR 20
TC 28
Z9 28
U1 5
U2 12
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 7
PY 2016
VL 374
IS 14
BP 1311
EP 1320
DI 10.1056/NEJMoa1516783
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3UW
UT WOS:000373425000005
PM 26842679
ER
PT J
AU Kernan, WN
Viscoli, CM
Furie, KL
Young, LH
Inzucchi, SE
Gorman, M
Guarino, PD
Lovejoy, AM
Peduzzi, PN
Conwit, R
Brass, LM
Schwartz, GG
Adams, HP
Berger, L
Carolei, A
Clark, W
Coull, B
Ford, GA
Kleindorfer, D
O'Leary, JR
Parsons, MW
Ringleb, P
Sen, S
Spence, JD
Tanne, D
Wang, D
Winder, TR
AF Kernan, W. N.
Viscoli, C. M.
Furie, K. L.
Young, L. H.
Inzucchi, S. E.
Gorman, M.
Guarino, P. D.
Lovejoy, A. M.
Peduzzi, P. N.
Conwit, R.
Brass, L. M.
Schwartz, G. G.
Adams, H. P., Jr.
Berger, L.
Carolei, A.
Clark, W.
Coull, B.
Ford, G. A.
Kleindorfer, D.
O'Leary, J. R.
Parsons, M. W.
Ringleb, P.
Sen, S.
Spence, J. D.
Tanne, D.
Wang, D.
Winder, T. R.
CA IRIS Trial Investigators
TI Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; IMPAIRED
GLUCOSE-TOLERANCE; HEALTH-CARE PROFESSIONALS; INSULIN-RESISTANCE;
NONDIABETIC PATIENTS; BLADDER-CANCER; MACROVASCULAR EVENTS; SECONDARY
PREVENTION; DIABETIC-PATIENTS
AB BACKGROUND
Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.
METHODS
In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.
RESULTS
By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003).
CONCLUSIONS
In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)
C1 [Kernan, W. N.; Viscoli, C. M.; Young, L. H.; Inzucchi, S. E.; Lovejoy, A. M.; Brass, L. M.; O'Leary, J. R.] Yale Univ, Sch Med, New Haven, CT USA.
[Guarino, P. D.; Peduzzi, P. N.; O'Leary, J. R.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Guarino, P. D.; Peduzzi, P. N.] Connecticut HealthCare Syst, Cooperat Studies Program Coordinating Ctr, VA, West Haven, CT USA.
[Furie, K. L.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Gorman, M.] Vermont Coll Med, Burlington, VT USA.
[Conwit, R.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Schwartz, G. G.] VA Med Ctr, Denver, CO USA.
[Schwartz, G. G.] Univ Colorado, Sch Med, Denver, CO USA.
[Adams, H. P., Jr.] Univ Iowa, Iowa City, IA USA.
[Berger, L.] Hop Charles LeMoyne, Greenfield Pk, IN USA.
[Spence, J. D.] Univ Western Ontario, London, ON N6A 3K7, Canada.
[Winder, T. R.] Ctr Neurol Res, Lethbridge, AB, Canada.
[Carolei, A.] Univ Aquila, I-67100 Laquila, Italy.
[Clark, W.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Coull, B.] Univ Arizona, Tucson, AZ USA.
[Ford, G. A.] Univ Oxford, Oxford OX1 2JD, Oxon, England.
[Ford, G. A.] Oxford Univ Hosp NHS Fdn Trust, Oxford, Oxon, England.
[Kleindorfer, D.] Univ Cincinnati, Cincinnati, OH USA.
[Parsons, M. W.] Univ Newcastle, John Hunter Hosp, New Lambton Hts, NSW, Australia.
[Ringleb, P.] Heidelberg Univ, Heidelberg, Germany.
[Sen, S.] Univ S Carolina, Sch Med, Columbia, SC 29208 USA.
[Tanne, D.] Tel Aviv Univ, Sheba Med Ctr, IL-69978 Tel Aviv, Israel.
[Wang, D.] Univ Illinois, Coll Med, OSF St Francis Med Ctr, Illinois Neurol Inst, Peoria, IL 61656 USA.
[Wang, D.] Univ Illinois, Coll Med, Dept Neurol, Peoria, IL 61656 USA.
RP Kernan, WN (reprint author), 2 Church St S,Suite 515, New Haven, CT 06519 USA.
EM walter.kernan@yale.edu
RI Spence, J. David/K-6396-2013;
OI Strain, William/0000-0002-6826-418X; Spence, J.
David/0000-0001-7478-1098; Groschel, Klaus/0000-0002-0244-6116
FU National Institute of Neurological Disorders and Stroke [U01NS044876];
Merck; Mifcor; Janssen; Sanofi; Poxel; Boehringer Ingelheim; Eli Lilly;
AstraZeneca; Novo Nordisk; Intarcia; Lexicon; Abbott; Millennium;
Cerenis; Roche; Resverlogix; Medicines Company; Lundbeck; Cerevast;
Pfizer; Athersys; Daiichi Sankyo; Covidien; Bayer; Bristol-Myers Squibb
FX Supported by a grant (U01NS044876) from the National Institute of
Neurological Disorders and Stroke. Pioglitazone and placebo were
provided by Takeda Pharmaceuticals International.; Dr. Young reports
receiving grant support through his institution from Merck and Mifcor;
Dr. Inzucchi, receiving fees for serving on advisory boards from Merck,
Janssen, Sanofi, Poxel, Boehringer Ingelheim, Eli Lilly, and
AstraZeneca, fees for serving on a data monitoring committee from Novo
Nordisk and Intarcia, and fees for serving on a steering committee from
Lexicon, serving as an expert witness on behalf of Takeda in a patent
litigation deposition, and participating in projects for which funding
for continuing medical education has been provided to Yale University by
Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Abbott, Merck, and
Sanofi; Dr. Peduzzi, receiving consulting fees from Millennium; Dr.
Schwartz, receiving grant support from Cerenis, Roche, Resverlogix,
Sanofi, and the Medicines Company; Dr. Ford, receiving fees for serving
on a trial steering committee from Lundbeck, fees for serving on a data
safety monitoring board from Cerevast, fees for serving on advisory
boards from Pfizer, Athersys, and Daiichi Sankyo, consulting fees from
Pfizer, and lecture fees and travel support from AstraZeneca and
Boehringer Ingelheim; Dr. Ringleb, receiving fees for serving on
advisory boards from Boehringer Ingelheim, Covidien, Bayer, and Daiichi
Sankyo and lecture fees and travel support from Boehringer Ingelheim,
Bayer, and Daiichi Sankyo; Dr. Spence, receiving consulting and lecture
fees from Bayer and Bristol-Myers Squibb, serving as an officer of and
having an equity interest in Vascularis, and performing contract
research for Bayer, Bristol-Myers Squibb, Pfizer, Acasti Pharma, POM
Wonderful, CVRx, AGA Medical, and W.L. Gore. No other potential conflict
of interest relevant to this article was reported.
NR 52
TC 74
Z9 74
U1 13
U2 27
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 7
PY 2016
VL 374
IS 14
BP 1321
EP 1331
DI 10.1056/NEJMoa1506930
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3UW
UT WOS:000373425000006
PM 26886418
ER
PT J
AU Li, J
Malley, JD
Andrew, AS
Karagas, MR
Moore, JH
AF Li, Jing
Malley, James D.
Andrew, Angeline S.
Karagas, Margaret R.
Moore, Jason H.
TI Detecting gene-gene interactions using a permutation-based random forest
method
SO BIODATA MINING
LA English
DT Article
DE Random forest; GWAS; Machine learning; Scale invariant
ID MULTIFACTOR DIMENSIONALITY REDUCTION; GENOME-WIDE ASSOCIATION; EPISTATIC
MODELS; COMPLEX TRAITS; LUNG-CANCER; DISEASE; RISK; POLYMORPHISMS;
NETWORKS; STRICT
AB Background: Identifying gene-gene interactions is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Here, we aimed at developing a permutation-based methodology relying on a machine learning method, random forest (RF), to detect gene-gene interactions. Our approach called permuted random forest (pRF) which identified the top interacting single nucleotide polymorphism (SNP) pairs by estimating how much the power of a random forest classification model is influenced by removing pairwise interactions.
Results: We systematically tested our approach on a simulation study with datasets possessing various genetic constraints including heritability, number of SNPs, sample size, etc. Our methodology showed high success rates for detecting the interaction SNP pair. We also applied our approach to two bladder cancer datasets, which showed consistent results with well-studied methodologies, such as multifactor dimensionality reduction (MDR) and statistical epistasis network (SEN). Furthermore, we built permuted random forest networks (PRFN), in which we used nodes to represent SNPs and edges to indicate interactions.
Conclusions: We successfully developed a scale-invariant methodology to detect pure gene-gene interactions based on permutation strategies and the machine learning method random forest. This methodology showed great potential to be used for detecting gene-gene interactions to study underlying genetic architectures in a scale-free way, which could be benefit to uncover the complex disease mechanisms.
C1 [Li, Jing] Dartmouth Coll, Geisel Sch Med, Dept Genet, Hanover, NH 03755 USA.
[Malley, James D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Andrew, Angeline S.; Karagas, Margaret R.] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, Hanover, NH 03755 USA.
[Moore, Jason H.] Univ Penn, Inst Biomed Informat, Philadelphia, PA 19104 USA.
[Moore, Jason H.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Moore, JH (reprint author), Univ Penn, Inst Biomed Informat, Philadelphia, PA 19104 USA.; Moore, JH (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
EM jhmoore@upenn.edu
FU National Institutes of Health (NIH) [LM009012, LM010098, LM011360,
EY022300, GM103506, GM103534, CA057494, P42ES0073737]
FX This work was supported by the National Institutes of Health (NIH) R01
grants LM009012, LM010098, LM011360, EY022300, GM103506, GM103534,
CA057494 and P42ES0073737.
NR 40
TC 5
Z9 5
U1 6
U2 24
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-0381
J9 BIODATA MIN
JI BioData Min.
PD APR 6
PY 2016
VL 9
AR 14
DI 10.1186/s13040-016-0093-5
PG 17
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DI7FC
UT WOS:000373663700001
PM 27053949
ER
PT J
AU Myles, IA
Reckhow, JD
Williams, KW
Sastalla, I
Frank, KM
Datta, SK
AF Myles, Ian A.
Reckhow, Jensen D.
Williams, Kelli W.
Sastalla, Inka
Frank, Karen M.
Datta, Sandip K.
TI A method for culturing Gram-negative skin microbiota
SO BMC MICROBIOLOGY
LA English
DT Article
DE Bacteriology; Skin; Microbiome; Culture techniques
ID DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY; IDENTIFICATION;
MEDIA
AB Background: Commensal Gram-negative (CGN) microbiota have been identified on human skin by DNA sequencing; however, methods to reliably culture viable Gram-negative skin organisms have not been previously described.
Results: Through the use of selective antibiotics and minimal media we developed methods to culture CGN from skin swabs. We identified several previously uncharacterized CGN at the species level by optimizing growth conditions and limiting the inhibitory effects of nutrient shock, temperature, and bacterial competition, factors that may have previously limited CGN isolation from skin cultures.
Conclusions: Our protocol will permit future functional studies on the influences of CGN on skin homeostasis and disease.
C1 [Myles, Ian A.; Reckhow, Jensen D.; Williams, Kelli W.; Sastalla, Inka; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Frank, Karen M.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Myles, IA (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mylesi@niaid.nih.gov
OI Datta, Sandip/0000-0003-0243-7815
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Disease
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of Allergy and
Infectious Disease.
NR 16
TC 1
Z9 1
U1 6
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD APR 6
PY 2016
VL 16
AR 60
DI 10.1186/s12866-016-0684-9
PG 6
WC Microbiology
SC Microbiology
GA DI6CD
UT WOS:000373585900001
PM 27052736
ER
PT J
AU Rhee, C
Kadri, SS
Danner, RL
Suffredini, AF
Massaro, AF
Kitch, BT
Lee, G
Klompas, M
AF Rhee, Chanu
Kadri, Sameer S.
Danner, Robert L.
Suffredini, Anthony F.
Massaro, Anthony F.
Kitch, Barrett T.
Lee, Grace
Klompas, Michael
TI Diagnosing sepsis is subjective and highly variable: a survey of
intensivists using case vignettes
SO CRITICAL CARE
LA English
DT Article
ID SEPTIC SHOCK; INTERNATIONAL GUIDELINES; CLINICAL-DATA; DEFINITIONS;
MANAGEMENT; CAMPAIGN; EPIDEMIOLOGY; DYSFUNCTION; CLAIMS; CARE
AB Background: Sepsis is the focus of national quality improvement programs and a recent public reporting measure from the Centers for Medicare and Medicaid Services. However, diagnosing sepsis requires interpreting nonspecific signs and can therefore be subjective. We sought to quantify interobserver variability in diagnosing sepsis.
Methods: We distributed five case vignettes of patients with suspected or confirmed infection and organ dysfunction to a sample of practicing intensivists. Respondents classified cases as systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or none of the above. Interobserver variability was calculated using Fleiss' kappa for the
five-level classification, and for answers dichotomized as severe sepsis/septic shock versus not-severe sepsis/septic shock and any sepsis category (sepsis, severe sepsis, or septic shock) versus not-sepsis.
Results: Ninety-four physicians completed the survey. Most respondents (88 %) identified as critical care specialists; other specialties included pulmonology (39 %), anesthesia (19 %), surgery (9 %), and emergency medicine (9 %). Respondents had been in practice for a median of 8 years, and 90 % practiced at academic hospitals. Almost all respondents (83 %) felt strongly or somewhat confident in their ability to apply the traditional consensus sepsis definitions. However, overall interrater agreement in sepsis diagnoses was poor (Fleiss' kappa 0.29). When responses were dichotomized into severe sepsis/septic shock versus not-severe sepsis/septic shock or any sepsis category versus not-sepsis, agreement was still poor (Fleiss' kappa 0.23 and 0.18, respectively). Seventeen percent of respondents classified one of the five cases as severe sepsis/septic shock, 27.7 % rated two cases, 33.0 % respondents rated three cases, 19.2 % rated four cases, and 3.2 % rated all five cases as severe sepsis/septic shock. Among respondents who felt strongly confident in their ability to use sepsis definitions (n = 45), agreement was no better (Fleiss' kappa 0.28 for the five-category classification, and Fleiss' kappa 0.21 for the dichotomized severe sepsis/septic shock classification). Cases were felt to be extremely or very realistic in 74 % of responses; only 3 % were deemed unrealistic.
Conclusions: Diagnosing sepsis is extremely subjective and variable. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, benchmarking, and reporting.
C1 [Rhee, Chanu; Lee, Grace; Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, 401 Pk Dr,Suite 401, Boston, MA USA.
[Rhee, Chanu; Lee, Grace; Klompas, Michael] Harvard Pilgrim Hlth Care Inst, 401 Pk Dr,Suite 401, Boston, MA USA.
[Rhee, Chanu; Massaro, Anthony F.; Klompas, Michael] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Kadri, Sameer S.; Danner, Robert L.; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kitch, Barrett T.] North Shore Med Ctr, Dept Med, Salem, MA USA.
RP Rhee, C (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 401 Pk Dr,Suite 401, Boston, MA USA.; Rhee, C (reprint author), Harvard Pilgrim Hlth Care Inst, 401 Pk Dr,Suite 401, Boston, MA USA.; Rhee, C (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM crhee1@partners.org
FU Department of Population Medicine, Harvard Medical School; Harvard
Pilgrim Health Care Institute; National Institutes of Health [T32
AI007061]
FX We thank the leadership of the U.S. Critical Illness and Injury Trials
Group, particularly Dr. Charles Cairns, for help in disseminating the
survey to the group. Gift cards for survey respondents were funded by
the Department of Population Medicine, Harvard Medical School and
Harvard Pilgrim Health Care Institute. CR received support from the
National Institutes of Health (grant T32 AI007061).
NR 24
TC 5
Z9 5
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD APR 6
PY 2016
VL 20
AR 89
DI 10.1186/s13054-016-1266-9
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA DI7HO
UT WOS:000373670400001
PM 27048508
ER
PT J
AU Rossi, PJ
Gunduz, A
Judy, J
Wilson, L
Machado, A
Giordano, JJ
Elias, WJ
Rossi, MA
Butson, CL
Fox, MD
McIntyre, CC
Pouratian, N
Swann, NC
de Hemptinne, C
Gross, RE
Chizeck, HJ
Tagliati, M
Lozano, AM
Goodman, W
Langevin, JP
Alterman, RL
Akbar, U
Gerhardt, GA
Grill, WM
Hallett, M
Herrington, T
Herron, J
van Horne, C
Kopell, BH
Lang, AE
Lungu, C
Martinez-Ramirez, D
Mogilner, AY
Molina, R
Opri, E
Otto, KJ
Oweiss, KG
Pathak, Y
Shukla, A
Shute, J
Sheth, SA
Shih, LC
Steinke, GK
Troster, AI
Vanegas, N
Zaghloul, KA
Cendejas-Zaragoza, L
Verhagen, L
Foote, KD
Okun, MS
AF Rossi, P. Justin
Gunduz, Aysegul
Judy, Jack
Wilson, Linda
Machado, Andre
Giordano, James J.
Elias, W. Jeff
Rossi, Marvin A.
Butson, Christopher L.
Fox, Michael D.
McIntyre, Cameron C.
Pouratian, Nader
Swann, Nicole C.
de Hemptinne, Coralie
Gross, Robert E.
Chizeck, Howard J.
Tagliati, Michele
Lozano, Andres M.
Goodman, Wayne
Langevin, Jean-Philippe
Alterman, Ron L.
Akbar, Umer
Gerhardt, Greg A.
Grill, Warren M.
Hallett, Mark
Herrington, Todd
Herron, Jeffrey
van Horne, Craig
Kopell, Brian H.
Lang, Anthony E.
Lungu, Codrin
Martinez-Ramirez, Daniel
Mogilner, Alon Y.
Molina, Rene
Opri, Enrico
Otto, Kevin J.
Oweiss, Karim G.
Pathak, Yagna
Shukla, Aparna
Shute, Jonathan
Sheth, Sameer A.
Shih, Ludy C.
Steinke, G. Karl
Troester, Alexander I.
Vanegas, Nora
Zaghloul, Kareem A.
Cendejas-Zaragoza, Leopoldo
Verhagen, Leonard
Foote, Kelly D.
Okun, Michael S.
TI Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A
Review of Emerging Issues and Technologies
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE deep brain stimulation; local field potentials; neuromodulation;
closed-loop; electrodes
ID POSTTRAUMATIC-STRESS-DISORDER; FOCUSED ULTRASOUND THALAMOTOMY;
PARKINSONS-DISEASE; ESSENTIAL TREMOR; SUBTHALAMIC NUCLEUS; TOURETTE
SYNDROME; MOVEMENT-DISORDERS; LATERAL HABENULA; GLOBUS-PALLIDUS;
DEPRESSION
AB The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.
C1 [Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Martinez-Ramirez, Daniel; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Shukla, Aparna; Shute, Jonathan; Foote, Kelly D.; Okun, Michael S.] Univ Florida, Dept Neurosci, Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32610 USA.
[Wilson, Linda] Int Technol Roadmap Semicond, Washington, DC USA.
[Machado, Andre] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA.
[Giordano, James J.] Georgetown Univ, Med Ctr, Dept Neurol, Neuroeth Studies Program, Washington, DC 20007 USA.
[Elias, W. Jeff] Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Neurol Surg & Neurol,Stereotact & Funct Neurosurg, Charlottesville, VA 22908 USA.
[Rossi, Marvin A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA.
[Butson, Christopher L.] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA.
[Fox, Michael D.; Alterman, Ron L.; Shih, Ludy C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[McIntyre, Cameron C.] Case Western Reserve Univ, Dept Biomed Engn, Sch Med, Cleveland, OH 44106 USA.
[Pouratian, Nader] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA.
[Swann, Nicole C.; de Hemptinne, Coralie] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gross, Robert E.] Emory Univ, Emory Clin, Atlanta, GA 30322 USA.
[Chizeck, Howard J.; Herron, Jeffrey] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA.
[Tagliati, Michele] Cedars Sinai Med Ctr, Dept Neurol, Movement Disorders Program, Los Angeles, CA 90048 USA.
[Lozano, Andres M.; Lang, Anthony E.] Univ Toronto, Dept Neurosurg, Toronto, ON, Canada.
[Goodman, Wayne; Kopell, Brian H.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Langevin, Jean-Philippe] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
[Akbar, Umer] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA.
[Gerhardt, Greg A.; van Horne, Craig] Univ Kentucky, Med Ctr, Lexington, KY USA.
[Grill, Warren M.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
[Hallett, Mark; Lungu, Codrin; Zaghloul, Kareem A.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Herrington, Todd] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Mogilner, Alon Y.] NYU, Dept Neurosurg, Ctr Neuromodulat, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA.
[Pathak, Yagna; Sheth, Sameer A.; Vanegas, Nora] Columbia Univ, Med Ctr, Neurol Inst, New York, NY USA.
[Steinke, G. Karl] Boston Sci Neuromodulat, Valencia, CA USA.
[Troester, Alexander I.] Barrow Neurol Inst, Dept Clin Neuropsychol, Phoenix, AZ 85013 USA.
RP Rossi, PJ (reprint author), Univ Florida, Dept Neurosci, Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32610 USA.
EM pjrossi@ufl.edu
RI Martinez-Ramirez, Daniel/H-2546-2016; Gunduz, Aysegul/Q-2336-2016;
OI Martinez-Ramirez, Daniel/0000-0001-8003-0610; Mogilner,
Alon/0000-0003-1493-0463
FU NICHD NIH HHS [T32 HD043730]; NINDS NIH HHS [R01 NS040894, R37 NS040894]
NR 103
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Z9 2
U1 13
U2 30
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD APR 6
PY 2016
VL 10
AR 119
DI 10.3389/fnins.2016.00119
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA DI4GU
UT WOS:000373459200001
PM 27092042
ER
PT J
AU Quaia, C
Optican, LM
Cumming, BG
AF Quaia, Christian
Optican, Lance M.
Cumming, Bruce G.
TI A Motion-from-Form Mechanism Contributes to Extracting Pattern Motion
from Plaids
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE flicker; motion; MT; unikinetic
ID VISUAL AREA MT; OCULAR-FOLLOWING RESPONSES; TRACKING EYE-MOVEMENTS;
SPATIOTEMPORAL ENERGY MODELS; PERCEIVED DIRECTION; 2-DIMENSIONAL
PATTERNS; FREQUENCY SELECTIVITY; TEMPORAL DYNAMICS; SPATIAL-FREQUENCY;
BINOCULAR-RIVALRY
AB Since the discovery of neurons selective for pattern motion direction in primate middle temporal area MT (Albright, 1984; Movshon et al., 1985), the neural computation of this signal has been the subject of intense study. The bulk of this work has explored responses to plaids obtained by summing two drifting sinusoidal gratings. Unfortunately, with these stimuli, many different mechanisms are similarly effective at extracting pattern motion. We devised a new set of stimuli, obtained by summing two random line stimuli with different orientations. This allowed several novel manipulations, including generating plaids that do not contain rigid 2D motion. Importantly, these stimuli do not engage most of the previously proposed mechanisms. We then recorded the ocular following responses that such stimuli induce in human subjects. We found that pattern motion is computed even with stimuli that do not cohere perceptually, including those without rigid motion, and even when the two gratings are presented separately to the two eyes. Moderate temporal and/or spatial separation of the gratings impairs the computation. We show that, of the models proposed so far, only those based on the intersection-of-constraints rule, embedding a motion-from-form mechanism (in which orientation signals are used in the computation of motion direction signals), can account for our results. At least for the eye movements reported here, a motion-from-form mechanism is thus involved in one of the most basic functions of the visual motion system: extracting motion direction from complex scenes.
C1 [Quaia, Christian; Optican, Lance M.; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Dept Hlth & Human Serv, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
RP Quaia, C (reprint author), NEI, Sensorimotor Res Lab, NIH, Dept Hlth & Human Serv, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM quaiac@nei.nih.gov
FU Intramural Research Program of the National Eye Institute/National
Institutes of Health/Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Eye Institute/National Institutes of Health/Department of
Health and Human Services. We thank Boris Sheliga for assistance in
running the experiments and two anonymous reviewers for their thoughtful
and constructive comments. We thank J. Anthony Movshon and Pascal
Wallisch for helpful discussions.
NR 82
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Z9 2
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 6
PY 2016
VL 36
IS 14
BP 3903
EP 3918
DI 10.1523/JNEUROSCI.3398-15.2016
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA DI4GC
UT WOS:000373457400003
PM 27053199
ER
PT J
AU Jocham, G
Brodersen, KH
Constantinescu, AO
Kahn, MC
Ianni, AM
Walton, ME
Rushworth, MFS
Behrens, TEJ
AF Jocham, Gerhard
Brodersen, Kay H.
Constantinescu, Alexandra O.
Kahn, Martin C.
Ianni, Angela M.
Walton, Mark E.
Rushworth, Matthew F. S.
Behrens, Timothy E. J.
TI Reward-Guided Learning with and without Causal Attribution
SO NEURON
LA English
DT Article
ID ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; DECISION-MAKING;
FRONTAL-CORTEX; BRAIN IMAGES; CHOICES; REINFORCEMENT; LESIONS; AMYGDALA;
NEURONS
AB When an organism receives a reward, it is crucial to know which of many candidate actions caused this reward. However, recent work suggests that learning is possible even when this most fundamental assumption is not met. We used novel reward-guided learning paradigms in two fMRI studies to show that humans deploy separable learning mechanisms that operate in parallel. While behavior was dominated by precise contingent learning, it also revealed hallmarks of noncontingent learning strategies. These learning mechanisms were separable behaviorally and neurally. Lateral orbitofrontal cortex supported contingent learning and reflected contingencies between outcomes and their causal choices. Amygdala responses around reward times related to statistical patterns of learning. Time-based heuristic mechanisms were related to activity in sensorimotor corticostriatal circuitry. Our data point to the existence of several learning mechanisms in the human brain, of which only one relies on applying known rules about the causal structure of the task.
C1 [Jocham, Gerhard; Brodersen, Kay H.; Constantinescu, Alexandra O.; Kahn, Martin C.; Ianni, Angela M.; Behrens, Timothy E. J.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England.
[Jocham, Gerhard] Otto Von Guericke Univ, Ctr Behav Brain Sci, Univ Pl 2, D-39106 Magdeburg, Germany.
[Jocham, Gerhard] Otto Von Guericke Univ, Fac Econ & Management, Univ Pl 2, D-39106 Magdeburg, Germany.
[Ianni, Angela M.] NIMH, Sect Integrat Neuroimaging, Clin & Translat Neurosci Branch, NIH,Intramural Res Program,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Brodersen, Kay H.; Walton, Mark E.; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
[Behrens, Timothy E. J.] UCL, Wellcome Trust Ctr Neuroimaging, 12 Queen Sq, London WC1N 3BG, England.
RP Jocham, G (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain, Oxford OX3 9DU, England.; Jocham, G (reprint author), Otto Von Guericke Univ, Ctr Behav Brain Sci, Univ Pl 2, D-39106 Magdeburg, Germany.; Jocham, G (reprint author), Otto Von Guericke Univ, Fac Econ & Management, Univ Pl 2, D-39106 Magdeburg, Germany.; Brodersen, KH (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
EM jocham@ovgu.de; khbrodersen@gmail.com
FU Federal State of Saxony Anhalt; Center for Behavioral Brain Sciences;
Wellcome Trust [099715/Z/12/Z, WT088312AIA, WT104765MA, WT090051MA];
James S. McDonnel Foundation award [JSMF220020372]
FX This work was supported by a grant from the Federal State of Saxony
Anhalt to G.J., project: Center for Behavioral Brain Sciences; a
Wellcome Trust 4-year PhD studentship (099715/Z/12/Z) to A.O.C. and a
Wellcome Trust Research Career Development Fellowship (WT088312AIA); a
Wellcome Trust Senior Research Fellowship (WT104765MA) and a James S.
McDonnel Foundation award (JSMF220020372) to T.E.J.B.; and a Wellcome
Trust Research Career Development Fellowship (WT090051MA) to M.E.W.
NR 44
TC 4
Z9 4
U1 8
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD APR 6
PY 2016
VL 90
IS 1
BP 177
EP 190
DI 10.1016/j.neuron.2016.02.018
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA DI5UK
UT WOS:000373565800018
PM 26971947
ER
PT J
AU Jain, S
Park, G
Sproule, TJ
Christianson, GJ
Leeth, CM
Wang, HS
Roopenian, DC
Morse, HC
AF Jain, Shweta
Park, Giljun
Sproule, Thomas J.
Christianson, Gregory J.
Leeth, Caroline M.
Wang, Hongsheng
Roopenian, Derry C.
Morse, Herbert C., III
TI Interleukin 6 Accelerates Mortality by Promoting the Progression of the
Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice
SO PLOS ONE
LA English
DT Article
ID CD4(+) T-CELLS; TOLL-LIKE RECEPTORS; ACTIVATE B-CELLS; MURINE LUPUS;
ANTI-DNA; IN-VIVO; IL-6; TLR7; DIFFERENTIATION; EXPRESSION
AB IL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4(+) T follicular helper cells (TFH). Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE). We previously reported that IL21 produced by T-FH plays a critical role in the development of the SLE-like disease of BXSB. Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB. Yaa mice. We report that survival of IL6-deficient BXSB. Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1). Importantly, the frequencies of T-FH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting T-FH in a signaling sequence that drives the lethal autoimmune disease of BXSB. Yaa mice.
C1 [Jain, Shweta; Wang, Hongsheng; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA.
[Park, Giljun; Sproule, Thomas J.; Christianson, Gregory J.; Roopenian, Derry C.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
[Park, Giljun] Univ Helsinki, Cent Hosp, Ctr Canc, Hematol Res Unit,Biomedicum Helsinki 1, Helsinki, Finland.
[Leeth, Caroline M.] Virginia Tech, Coll Agr & Life Sci, Dept Anim & Poultry Sci, Blacksburg, VA USA.
RP Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA.; Roopenian, DC (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM dcr@jax.org; hmorse@niaid.nih.gov
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases (NIAID); Alliance for Lupus Research
FX This work was supported in part by the Intramural Research Program of
the NIH, National Institute of Allergy and Infectious Diseases (NIAID),
and by the Alliance for Lupus Research.
NR 60
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 6
PY 2016
VL 11
IS 4
AR e0153059
DI 10.1371/journal.pone.0153059
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI6IX
UT WOS:000373603500090
PM 27050763
ER
PT J
AU Oga, EA
Schumaker, LM
Alabi, BS
Obaseki, D
Umana, A
Bassey, IA
Ebughe, G
Oluwole, O
Akeredolu, T
Adebamowo, SN
Dakum, P
Cullen, K
Adebamowo, CA
AF Oga, Emmanuel A.
Schumaker, Lisa M.
Alabi, Biodun Sulyman
Obaseki, Darlington
Umana, Aniefon
Bassey, Ima-Abasi
Ebughe, Godwin
Oluwole, Olabode
Akeredolu, Teniola
Adebamowo, Sally N.
Dakum, Patrick
Cullen, Kevin
Adebamowo, Clement A.
TI Paucity of HPV-Related Head and Neck Cancers (HNC) in Nigeria
SO PLOS ONE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; UNITED-STATES;
ALCOHOL-DRINKING; INCIDENCE TRENDS; TOBACCO SMOKING; ORAL SEX;
PREVALENCE; RISK; ADOLESCENTS
AB Introduction
The burden of HPV-related Head and Neck Cancers (HNC) has been rising in the U.S. and other developed countries but this trend has not been reported in Africa. Objective of study was to evaluate the prevalence of HPV infection in HNC cancer cases seen between 1990 and 2011 at the tertiary health care institutions in Nigeria.
Methods
We retrieved 149 head and neck cancer formalin fixed, paraffin embedded tumor specimens diagnosed between 1990 and 2011 from four teaching hospitals in Nigeria. One hundred and twenty-three blocks (83%) contained appropriate HNC for analysis while DNA extraction was successful in 60% (90/149). PCR amplification was successful in 33% (49/149) and Linear Array genotyping for HPV was successful in 11% (17/149) of these cases. These were in tumors from the larynx (6), cervical lymph nodes (3), nasal cavity (2), parotid (1), palate (1), maxillary sinus (1) and mandible (1). Two cases were non-specific and none were from the oropharynx. Histologically, 41% (7/17) of the successfully genotyped blocks were squamous cell carcinomas (larynx 6, maxillary sinus 1).
Results and Conclusion
We were unable to detect HPV in any of the HNC samples in our study. Our result may suggest that there is a low prevalence of HPV-related HNC among the adult population in Nigeria. Our results provide a benchmark to compare future incidence of HPV-related HNC in this community in future. We had significant analytical challenges from possible poor tissue processing and urge that future studies should prospectively collect samples and ensure high quality sample processing.
C1 [Oga, Emmanuel A.; Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Oga, Emmanuel A.; Akeredolu, Teniola; Adebamowo, Sally N.; Dakum, Patrick; Adebamowo, Clement A.] Inst Human Virol Nigeria, Off Res Training & Strateg Informat, Abuja, Fct, Nigeria.
[Schumaker, Lisa M.; Cullen, Kevin; Adebamowo, Clement A.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Alabi, Biodun Sulyman] Univ Ilorin Teaching Hosp, Dept Ear Nose & Throat Head & Neck Surg, Ilorin, Kwara State, Nigeria.
[Obaseki, Darlington] Univ Benin Teaching Hosp, Benin, Edo State, Nigeria.
[Umana, Aniefon; Bassey, Ima-Abasi; Ebughe, Godwin] Univ Calabar Teaching Hosp, Calabar, Cross River Sta, Nigeria.
[Oluwole, Olabode] Univ Abuja Teaching Hosp, Abuja, Fct, Nigeria.
[Adebamowo, Sally N.; Adebamowo, Clement A.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Adebamowo, Sally N.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Oga, EA (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.; Oga, EA (reprint author), Inst Human Virol Nigeria, Off Res Training & Strateg Informat, Abuja, Fct, Nigeria.
EM eoga@umaryland.edu
OI Adebamowo, Sally/0000-0003-4713-2433; Oga, Emmanuel/0000-0002-0744-5681
FU NCI/NIH [D43CA153792-01]
FX The project described was supported by Grant Number D43CA153792-01 (PI -
Adebamowo) from the NCI/NIH. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health.
NR 54
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U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 6
PY 2016
VL 11
IS 4
AR e0152828
DI 10.1371/journal.pone.0152828
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI6IX
UT WOS:000373603500057
PM 27050815
ER
PT J
AU Bentolila, LA
Prakash, R
Mihic-Probst, D
Wadehra, M
Kleinman, HK
Carmichael, TS
Peault, B
Barnhill, RL
Lugassy, C
AF Bentolila, Laurent A.
Prakash, Roshini
Mihic-Probst, Daniela
Wadehra, Madhuri
Kleinman, Hynda K.
Carmichael, Thomas S.
Peault, Bruno
Barnhill, Raymond L.
Lugassy, Claire
TI Imaging of Angiotropism/Vascular Co-Option in a Murine Model of Brain
Melanoma: Implications for Melanoma Progression along Extravascular
Pathways
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MIGRATORY METASTASIS; MALIGNANT-MELANOMA; CELL INVASION; CANCER-CELLS;
STEM-CELLS; TUMORS; ANGIOGENESIS; PLASTICITY; GROWTH; MICROENVIRONMENT
AB Angiotropism/pericytic mimicry and vascular co-option involve tumor cell interactions with the abluminal vascular surface. These two phenomena may be closely related. However, investigations of the two processes have developed in an independent fashion and different explanations offered as to their biological nature. Angiotropism describes the propensity of tumor cells to spread distantly via continuous migration along abluminal vascular surfaces, or extravascular migratory metastasis (EVMM). Vascular co-option has been proposed as an alternative mechanism by which tumors cells may gain access to a blood supply. We have used a murine brain melanoma model to analyze the interactions of GFP human melanoma cells injected into the mouse brain with red fluorescent lectin-labeled microvascular channels. Results have shown a striking spread of melanoma cells along preexisting microvascular channels and features of both vascular co-option and angiotropism/pericytic mimicry. This study has also documented the perivascular expression of Serpin B2 by angiotropic melanoma cells in the murine brain and in human melanoma brain metastases. Our findings suggest that vascular cooption and angiotropism/pericytic mimicry are closely related if not identical processes. Further studies are needed in order to establish whether EVMM is an alternative form of cancer metastasis in addition to intravascular cancer dissemination.
C1 [Bentolila, Laurent A.] California NanoSyst Inst, Los Angeles, CA 90095 USA.
[Bentolila, Laurent A.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Prakash, Roshini; Carmichael, Thomas S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Mihic-Probst, Daniela] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland.
[Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Kleinman, Hynda K.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Peault, Bruno] Univ Calif Los Angeles, David Geffen Sch Med, Orthoped Hosp, Res Ctr, Los Angeles, CA 90095 USA.
[Peault, Bruno] Univ Calif Los Angeles, David Geffen Sch Med, Broad Stem Cell Ctr, Los Angeles, CA 90095 USA.
[Peault, Bruno] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh, Midlothian, Scotland.
[Peault, Bruno] Univ Edinburgh, BHF Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
[Barnhill, Raymond L.] Inst Curie, Dept Pathol, Paris, France.
[Barnhill, Raymond L.] Univ Paris 05, Paris, France.
[Lugassy, Claire] Inst Curie, Dept Translat Res, Paris, France.
RP Barnhill, RL (reprint author), Inst Curie, Dept Pathol, Paris, France.; Barnhill, RL (reprint author), Univ Paris 05, Paris, France.
EM raymond.barnhill@gmail.com
FU NIH/National Center for Advancing Translational Science UCLA CTSI Grant
[UL1TR000124]
FX Confocal imaging was performed at the California NanoSystems Institute
(CNSI) Advanced Light Microscopy/Spectroscopy Shared Resource Facility
at UCLA with support from a NIH/National Center for Advancing
Translational Science UCLA CTSI Grant (UL1TR000124). The authors also
thanks Olivier Brun from Leica Microsystems for providing access to the
SP8 X microscope used in Figure 3 and Supplementary Movie S1.
NR 46
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U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD APR 6
PY 2016
VL 6
AR 23834
DI 10.1038/srep23834
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI3WJ
UT WOS:000373430500001
PM 27048955
ER
PT J
AU Habes, M
Janowitz, D
Erus, G
Toledo, JB
Resnick, SM
Doshi, J
Van der Auwera, S
Wittfeld, K
Hegenscheid, K
Hosten, N
Biffar, R
Homuth, G
Volzke, H
Grabe, HJ
Hoffmann, W
Davatzikos, C
AF Habes, M.
Janowitz, D.
Erus, G.
Toledo, J. B.
Resnick, S. M.
Doshi, J.
Van der Auwera, S.
Wittfeld, K.
Hegenscheid, K.
Hosten, N.
Biffar, R.
Homuth, G.
Volzke, H.
Grabe, H. J.
Hoffmann, W.
Davatzikos, C.
TI Advanced brain aging: relationship with epidemiologic and genetic risk
factors, and overlap with Alzheimer disease atrophy patterns
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID MIDLIFE BLOOD-PRESSURE; GRAY-MATTER VOLUME; COGNITIVE DECLINE;
SPATIAL-PATTERNS; OLDER-ADULTS; SEGMENTATION; DEMENTIA; MRI;
CLASSIFICATION; METAANALYSIS
AB We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P < 0.05), anti-hypertensive (P < 0.05), anti-diabetic drug use (men P < 0.05, women P = 0.06) and waist circumference for the male cohort (P < 0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q < 0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.
C1 [Habes, M.; Volzke, H.; Hoffmann, W.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Habes, M.; Erus, G.; Doshi, J.; Davatzikos, C.] Univ Penn, Dept Radiol, Ctr Biomed Image Comp & Analyt, 3700 Hamilton Walk, Philadelphia, PA 19104 USA.
[Habes, M.; Janowitz, D.; Van der Auwera, S.; Grabe, H. J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat, Greifswald, Germany.
[Toledo, J. B.] Univ Penn, Dept Pathol & Lab Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA USA.
[Resnick, S. M.] NIA, Lab Behav Neurosci, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wittfeld, K.; Grabe, H. J.; Hoffmann, W.] German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany.
[Hegenscheid, K.; Hosten, N.] Ernst Moritz Arndt Univ Greifswald, Dept Radiol, Greifswald, Germany.
[Biffar, R.] Ernst Moritz Arndt Univ Greifswald, Dept Dent, Greifswald, Germany.
[Homuth, G.] Ernst Moritz Arndt Univ Greifswald, Inst Genet & Funct Genom, Greifswald, Germany.
RP Habes, M (reprint author), Univ Penn, Dept Radiol, Ctr Biomed Image Comp & Analyt, 3700 Hamilton Walk, Philadelphia, PA 19104 USA.
EM habesm@uphs.upenn.edu
RI Habes, Mohamad/M-2865-2016;
OI Habes, Mohamad/0000-0001-9447-5805; Janowitz,
Deborah/0000-0003-4324-9298; Toledo, Jon/0000-0003-4366-9268
FU Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103,
01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of
the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare,
Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; NIH
[R01-AG014971]; 'Alfried Krupp von Bohlen und Halbach' foundation
FX SHIP is part of the Community Medicine Research net of the University of
Greifswald, Germany, which is funded by the Federal Ministry of
Education and Research (grants no. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the
Ministry of Cultural Affairs and the Social Ministry of the Federal
State of Mecklenburg-West Pomerania. Genome-wide data in SHIP and MRI
scans in SHIP and SHIP-TREND have been supported by a joint grant from
Siemens Healthcare, Erlangen, Germany and the Federal State of
Mecklenburg-West Pomerania. Genome-wide genotyping in SHIP-TREND-0 was
supported by the Federal Ministry of Education and Research (grant no.
03ZIK012). This work has been supported in part by NIH (grant no.
R01-AG014971). MH was supported by 'Alfried Krupp von Bohlen und
Halbach' foundation.
NR 55
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Z9 1
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD APR 5
PY 2016
VL 6
AR e775
DI 10.1038/tp.2016.39
PG 8
WC Psychiatry
SC Psychiatry
GA DN8BJ
UT WOS:000377303600005
PM 27045845
ER
PT J
AU Galiatsatos, P
Win, T
Monti, J
Johnston, P
Herzog, W
Trost, J
Hwang, CW
Wang, NY
Silber, H
AF Galiatsatos, Panagis
Win, Theingi
Monti, Jennifer
Johnston, Peter
Herzog, William
Trost, Jeffrey
Hwang, Chao-Wei
Wang, Nae-Yuh
Silber, Harry
TI A NONINVASIVE HAND-HELD DEVICE IDENTIFIES ELEVATED LEFT VENTRICULAR
FILLING PRESSURE USING FINGER PHOTOPLETHYSMOGRAPHY DURING THE VALSALVA
MANEUVER
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 Johns Hopkins Med, Baltimore, MD USA.
NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1171-070
BP 1427
EP 1427
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702273
ER
PT J
AU Mehta, NN
Kabbany, MT
Ahlman, M
Rodante, J
Lerman, J
Aberra, T
Silverman, J
Aridi, T
Dahiya, A
Bluemke, D
Playford, M
Joshi, A
AF Mehta, Nehal N.
Kabbany, Mohammad Tarek
Ahlman, Mark
Rodante, Justin
Lerman, Joseph
Aberra, Tsion
Silverman, Joanna
Aridi, Tarek
Dahiya, Asha
Bluemke, David
Playford, Martin
Joshi, Aditya
TI DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI:
FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE
INITIATIVE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 [Mehta, Nehal N.; Kabbany, Mohammad Tarek; Ahlman, Mark; Rodante, Justin; Lerman, Joseph; Aberra, Tsion; Silverman, Joanna; Aridi, Tarek; Dahiya, Asha; Bluemke, David; Playford, Martin; Joshi, Aditya] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1182-223
BP 1692
EP 1692
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702538
ER
PT J
AU Joshi, AA
Kabbany, MT
Ahlman, M
Lerman, J
Aberra, T
Natarajan, B
Salahuddin, T
Rodante, J
Playford, M
Chen, M
Bluemke, D
Mehta, N
AF Joshi, Aditya A.
Kabbany, Mohammad Tarek
Ahlman, Mark
Lerman, Joseph
Aberra, Tsion
Natarajan, Balaji
Salahuddin, Taufiq
Rodante, Justin
Playford, Martin
Chen, Marcus
Bluemke, David
Mehta, Nehal
TI AORTIC VASCULAR INFLAMMATION BY 18-FDG PET/MRI IS RELATED TO CORONARY
PLAQUE BURDEN BY QUANTITATIVE CORONARY CT ANGIOGRAPHY IN PSORIASIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 [Joshi, Aditya A.; Kabbany, Mohammad Tarek; Ahlman, Mark; Lerman, Joseph; Aberra, Tsion; Natarajan, Balaji; Salahuddin, Taufiq; Rodante, Justin; Playford, Martin; Chen, Marcus; Bluemke, David; Mehta, Nehal] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1230-237
BP 1754
EP 1754
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702600
ER
PT J
AU Vargas, JD
Manichaikul, A
Liu, CY
Rich, S
Post, W
Judge, D
Bluemke, D
AF Vargas, Jose D.
Manichaikul, Ani
Liu, Chia-Ying
Rich, Stephen
Post, Wendy
Judge, Daniel
Bluemke, David
TI COMMON GENETIC VARIANTS AND LEFT VENTRICULAR STRUCTURE IN THE
MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 [Vargas, Jose D.; Manichaikul, Ani; Liu, Chia-Ying; Rich, Stephen; Post, Wendy; Judge, Daniel; Bluemke, David] NIH, Bldg 10, Bethesda, MD 20892 USA.
OI Manichaikul, Ani/0000-0002-5998-795X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1263-261
BP 1835
EP 1835
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702681
ER
PT J
AU Mehta, NN
Natarajan, B
Playford, M
Lerman, J
Kabbany, MT
Aberra, T
Ng, Q
Teague, H
Rodante, J
Joshi, A
AF Mehta, Nehal N.
Natarajan, Balaji
Playford, Martin
Lerman, Joseph
Kabbany, Mohammad Tarek
Aberra, Tsion
Qimin Ng
Teague, Heather
Rodante, Justin
Joshi, Aditya
TI SMALL DENSE LOW-DENSITY LIPOPROTEIN (LDL) PARTICLE NUMBER PREDICTS
VASCULAR INFLAMMATION INDEPENDENT OF TRADITIONAL LIPID CARDIOVASCULAR
RISK FACTORS IN PSORIASIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 [Mehta, Nehal N.; Natarajan, Balaji; Playford, Martin; Lerman, Joseph; Kabbany, Mohammad Tarek; Aberra, Tsion; Qimin Ng; Teague, Heather; Rodante, Justin; Joshi, Aditya] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1156-376
BP 1916
EP 1916
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702762
ER
PT J
AU Lerman, J
Joshi, A
Rodante, J
Aberra, T
Kabbany, MT
Salahuddin, T
Ng, Q
Silverman, J
Chen, M
Bluemke, D
Playford, M
Mehta, N
AF Lerman, Joseph
Joshi, Aditya
Rodante, Justin
Aberra, Tsion
Kabbany, Mohammad Tarek
Salahuddin, Taufiq
Qimin Ng
Silverman, Joanna
Chen, Marcus
Bluemke, David
Playford, Martin
Mehta, Nehal
TI IMPROVEMENT IN PSORIASIS SKIN DISEASE SEVERITY IS ASSOCIATED WITH
REDUCTION OF CORONARY PLAQUE BURDEN
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 [Lerman, Joseph; Joshi, Aditya; Rodante, Justin; Aberra, Tsion; Kabbany, Mohammad Tarek; Salahuddin, Taufiq; Qimin Ng; Silverman, Joanna; Chen, Marcus; Bluemke, David; Playford, Martin; Mehta, Nehal] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1156-378
BP 1918
EP 1918
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702764
ER
PT J
AU Albaeni, A
Beydoun, MA
Eid, S
Beydoun, HA
Chandra-Strobos, N
AF Albaeni, Aiham
Beydoun, May A.
Eid, Shaker
Beydoun, Hind A.
Chandra-Strobos, Nisha
TI RACE AND OUTCOMES FOLLOWING OUT OF HOSPITAL CARDIAC ARREST: THE CHANGING
PLAYING FIELD 2002 TO 2012
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 65th Annual Scientific Session and Expo of the
American-College-of-Cardiology (ACC)
CY APR 02-04, 2016
CL Chicago, IL
SP Amer Coll Cardiol
C1 Johns Hopkins Univ, Baltimore, MD USA.
NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
SU S
MA 1271-388
BP 2030
EP 2030
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK8PH
UT WOS:000375188702876
ER
PT J
AU Mehta, FF
Son, J
Hewitt, SC
Jang, EJ
Lydon, JP
Korach, KS
Chung, SH
AF Mehta, Fabiola F.
Son, Jieun
Hewitt, Sylvia C.
Jang, Eunjung
Lydon, John P.
Korach, Kenneth S.
Chung, Sang-Hyuk
TI Distinct functions and regulation of epithelial progesterone receptor in
the mouse cervix, vagina, and uterus
SO ONCOTARGET
LA English
DT Article
DE progesterone receptor; estrogen receptor alpha; epithelium; female
reproductive tract; mouse model; Pathology Section
ID FEMALE REPRODUCTIVE-TRACT; PARACRINE REGULATION; MAMMARY-GLAND;
BREAST-CANCER; ESTROUS-CYCLE; ER-ALPHA; IN-VIVO; GENE; BINDING; MICE
AB While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P-4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P-4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor alpha (ER alpha) in the female reproductive tracts. Using knock-in mouse models expressing ERa mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERa were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERa AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERa DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERa. Epithelial ERa was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.
C1 [Mehta, Fabiola F.; Son, Jieun; Jang, Eunjung; Chung, Sang-Hyuk] Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA.
[Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
[Lydon, John P.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Chung, SH (reprint author), Univ Houston, Dept Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA.
EM schung@uh.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU Cancer Prevention and Research Institute of Texas [RP120617]; NIH [R01
CA188646, R01 HD042311]; Division of Intramural Research of the NIH,
National Institute of Environmental Health Sciences Project
[1ZIAES070065]
FX The work was supported by the Cancer Prevention and Research Institute
of Texas grant RP120617 (S.-H.C) and NIH grants R01 CA188646 (S.-H.C.)
and R01 HD042311 (J.P.L.) and by the Division of Intramural Research of
the NIH, National Institute of Environmental Health Sciences Project
1ZIAES070065 (S.C.H. and K.S.K.).
NR 39
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Z9 1
U1 2
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 5
PY 2016
VL 7
IS 14
BP 17455
EP 17467
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL5TE
UT WOS:000375699000016
PM 27007157
ER
PT J
AU Symonds, JM
Ohm, AM
Tan, AC
Reyland, ME
AF Symonds, Jennifer M.
Ohm, Angela M.
Tan, Aik-Choon
Reyland, Mary E.
TI PKC delta regulates integrin alpha(V)beta(3) expression and transformed
growth of K-ras dependent lung cancer cells
SO ONCOTARGET
LA English
DT Article
DE PKC delta; lung cancer; integrins; KRAS; anchorage independent growth
ID KINASE-C-DELTA; ANOIKIS RESISTANCE; NADPH OXIDASE; CYCLE ARREST;
IN-VIVO; ALPHA; ACTIVATION; SURVIVAL; PHOSPHORYLATION; INVASIVENESS
AB We have previously shown that Protein Kinase C delta (PKC delta) functions as a tumor promoter in non-small cell lung cancer (NSCLC), specifically in the context of K-ras addiction. Here we define a novel PKC delta -> integrin alpha(V)beta(3) -> Extracellular signal-Regulated Kinase (ERK) pathway that regulates the transformed growth of K-ras dependent NSCLC cells. To explore how PKC delta regulates tumorigenesis, we performed mRNA expression analysis in four KRAS mutant NSCLC cell lines that stably express scrambled shRNA or a PKC delta targeted shRNA. Analysis of PKC delta-dependent mRNA expression identified 3183 regulated genes, 210 of which were specifically regulated in K-ras dependent cells. Genes that regulate extracellular matrix and focal adhesion pathways were most highly represented in this later group. In particular, expression of the integrin pair, alpha(V)beta(3), was specifically reduced in K-ras dependent cells with depletion of PKC delta, and correlated with reduced ERK activation and reduced transformed growth as assayed by clonogenic survival. Re-expression of PKC delta restored ITGAV and ITGB3 mRNA expression, ERK activation and transformed growth, and this could be blocked by pretreatment with a alpha(V)beta(3) function-blocking antibody, demonstrating a requirement for integrin alpha(V)beta(3) downstream of PKC delta. Similarly, expression of integrin alpha(V) restored ERK activation and transformed growth in PKC delta depleted cells, and this could also be inhibited by pretreatment with PD98059. Our studies demonstrate an essential role for alpha(V)beta(3) and ERK signaling downstream of PKC delta in regulating the survival of K-ras dependent NSCLC cells, and identify PKC delta as a novel therapeutic target for the subset of NSCLC patients with K-ras dependent tumors.
C1 [Symonds, Jennifer M.] Grad Sch, Program Canc Biol, Aurora, CO USA.
[Ohm, Angela M.; Reyland, Mary E.] Sch Dent Med, Dept Craniofacial Biol, Aurora, CO USA.
[Tan, Aik-Choon] Univ Colorado Anschutz Med Campus, Sch Med, Dept Med Oncol, Aurora, CO USA.
[Symonds, Jennifer M.] NIDCR, Matrix & Morphogenesis Sect, NIH, Bethesda, MD USA.
RP Reyland, ME (reprint author), Sch Dent Med, Dept Craniofacial Biol, Aurora, CO USA.
EM Mary.Reyland@ucdenver.edu
FU United Against Lung Cancer research award; NIH Lung SPORE grant [P50
CA58187, R01DE015648]
FX This work was supported by a United Against Lung Cancer research award,
a pilot grant from NIH Lung SPORE grant P50 CA58187, and R01DE015648 to
MER.
NR 51
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U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 5
PY 2016
VL 7
IS 14
BP 17905
EP 17919
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL5TE
UT WOS:000375699000050
PM 26918447
ER
PT J
AU De Luca, P
Dalton, GN
Scalise, GD
Moiola, CP
Porretti, J
Massillo, C
Kordon, E
Gardner, K
Zalazar, F
Flumian, C
Todaro, L
Vazquez, ES
Meiss, R
De Siervi, A
AF De Luca, Paola
Dalton, Guillermo N.
Scalise, Georgina D.
Moiola, Cristian P.
Porretti, Juliana
Massillo, Cintia
Kordon, Edith
Gardner, Kevin
Zalazar, Florencia
Flumian, Carolina
Todaro, Laura
Vazquez, Elba S.
Meiss, Roberto
De Siervi, Adriana
TI CtBP1 associates metabolic syndrome and breast carcinogenesis targeting
multiple miRNAs
SO ONCOTARGET
LA English
DT Article
DE CtBP1; metabolic syndrome; high fat diet; breast cancer; miRNAs
ID MAMMARY-GLAND DEVELOPMENT; CANCER RISK; HIGH-FAT; PROSTATE-CANCER;
PROGRESSION; PREVENTION; CELLS; TUMORIGENESIS; APOPTOSIS; EXPOSURE
AB Metabolic syndrome (MeS) has been identified as a risk factor for breast cancer. C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. High fat diet (HFD) increases intracellular NADH. We investigated the effect of CtBP1 hyperactivation by HFD intake on mouse breast carcinogenesis. We generated a MeS-like disease in female mice by chronically feeding animals with HFD. MeS increased postnatal mammary gland development and generated prominent duct patterns with markedly increased CtBP1 and Cyclin D1 expression. CtBP1 induced breast cancer cells proliferation. Serum from animals with MeS enriched the stem-like/progenitor cell population from breast cancer cells. CtBP1 increased breast tumor growth in MeS mice modulating multiple genes and miRNA expression implicated in cell proliferation, progenitor cells phenotype, epithelial to mesenchymal transition, mammary development and cell communication in the xenografts. These results define a novel function for CtBP1 in breast carcinogenesis.
C1 [De Luca, Paola; Dalton, Guillermo N.; Scalise, Georgina D.; Moiola, Cristian P.; Porretti, Juliana; Massillo, Cintia; Zalazar, Florencia; De Siervi, Adriana] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt IBYME, Lab Oncol Mol & Nuevos Blancos Terapeut, RA-1033 Buenos Aires, DF, Argentina.
[Kordon, Edith] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Fisiol Biol Mol & Celular, Buenos Aires, DF, Argentina.
[Kordon, Edith] Consejo Nacl Invest Cient & Tecn, Inst Fisiol Biol Mol & Neurociencias IFIBYNE, RA-1033 Buenos Aires, DF, Argentina.
[Gardner, Kevin] NCI, NIH, Bethesda, MD 20892 USA.
[Flumian, Carolina; Todaro, Laura] Univ Buenos Aires, Inst Oncol AH Roffo, Area Invest, Buenos Aires, DF, Argentina.
[Vazquez, Elba S.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, Lab Inflamac & Canc,IQUIBICEN,CONICET, Buenos Aires, DF, Argentina.
[Meiss, Roberto] Acad Nacl Med Buenos Aires, Inst Estudios Oncol, Dept Patol, Buenos Aires, DF, Argentina.
RP De Siervi, A (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt IBYME, Lab Oncol Mol & Nuevos Blancos Terapeut, RA-1033 Buenos Aires, DF, Argentina.
EM adrianadesiervi@gmail.com
FU Argentinean Agency of Science and Technology (ANPCyT) [PICT 2014-324,
PICT 2013-2151, PICT 2012-00374]; Fundacion Williams (Argentina);
Fundacion Rene Baron (Argentina)
FX This research was supported by the Argentinean Agency of Science and
Technology (ANPCyT PICT 2014-324; ANPCyT PICT 2013-2151; ANPCyT PICT
2012-00374). We thank the Fundacion Williams (Argentina) and Fundacion
Rene Baron (Argentina) for their support. Part of the figures in this
work was completed for the undergraduate thesis of G.N. Dalton.
NR 43
TC 0
Z9 0
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD APR 5
PY 2016
VL 7
IS 14
BP 18798
EP 18811
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL5TE
UT WOS:000375699000121
PM 26933806
ER
PT J
AU Yuan, L
Zhi, W
Liu, YS
Smiley, E
Gallagher, D
Chen, X
Dietrich, AM
Zhang, HS
AF Yuan, Li
Zhi, Wei
Liu, Yangsheng
Smiley, Elizabeth
Gallagher, Daniel
Chen, Xi
Dietrich, Andrea M.
Zhang, Husen
TI Degradation of cis- and trans-(4-methylcyclohexyl) methanol in activated
sludge
SO JOURNAL OF HAZARDOUS MATERIALS
LA English
DT Article
DE West Virginia Chemical Spill; Crude (4-methylcyclohexyl)methanol;
Activated sludge; Biodegradation kinetics; Transformation products
ID WATER TREATMENT PLANTS; VOLATILE FATTY-ACIDS; FLOW CONSTRUCTED WETLAND;
VIRGINIA CHEMICAL SPILL; WEST-VIRGINIA; WASTE-WATER; COMMUNITY
COMPOSITION; NITRATE REDUCTION; FUNCTIONAL GENES; NITROGEN REMOVAL
AB Crude (4-methylcyclohexyl)methanol (MCHM) caused extensive contamination of drinking water, wastewater, and the environment during the 2014 West Virginia Chemical Spill. However, information related to the environmental degradation of cis- and trans-4-MCHM, the main components of the crude 4-MCHM mixture, remains largely unknown. This study is among the first to investigate the degradation kinetics and transformation of 4-MCHM isomers in activated sludge. The 4-MCHM loss was mainly due to biodegradation to form carbon dioxide (CO2), plus acetic, propionic, isobutyric, and isovaleric acids with little contribution from adsorption. The biodegradation of 4-MCHM isomers followed the first-order kinetic model with half-lives higher than 0.50 days. Nitrate augmented the degradation of 4-MCHM isomers, while glucose and acetate decreased their degradation. One 4-MCHM-degrading bacterium isolated from activated sludge was identified as Acinetobacter bouvetii strain EU40 based on 16S rRNA gene sequences. This study will enhance the prediction of the environmental fate of 4-MCHM in water treatment systems. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Yuan, Li; Zhi, Wei; Smiley, Elizabeth; Gallagher, Daniel; Dietrich, Andrea M.; Zhang, Husen] Virginia Polytech Inst & State Univ, Dept Civil & Environm Engn, Blacksburg, VA 24061 USA.
[Yuan, Li; Liu, Yangsheng] Peking Univ, Coll Environm Sci & Engn, Beijing 100871, Peoples R China.
[Chen, Xi] Columbia Univ, Dept Earth & Environm Engn, New York, NY 10027 USA.
RP Zhang, HS (reprint author), NCI, Bldg 37,Room 4137,37 Convent Dr, Bethesda, MD 20892 USA.
EM husen@vt.edu
RI Chen, Xi/B-1539-2008
OI Chen, Xi/0000-0002-2428-180X
FU Virginia Tech College of Engineering; China Scholarship Council (CSC);
National Natural Science Foundation of China [11172231, 11372241]; AFOSR
[FA9550-12-1-0159]; ARPA-E [DE-AR0000396]; National Science Foundation,
CBET [1424234]
FX This work was supported by Dr. Zhang's startup funds provided by
Virginia Tech College of Engineering. Li Yuan acknowledges support from
the China Scholarship Council (CSC) visiting scholarship. The work of Xi
Chen was supported by National Natural Science Foundation of China
(11172231 and 11372241), AFOSR (FA9550-12-1-0159), and ARPA-E
(DE-AR0000396). The research was performed in conjunction with National
Science Foundation, CBET Award # 1424234 in which the headspace and
GC-MS methods for 4-MCHM were developed.
NR 55
TC 1
Z9 1
U1 5
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3894
EI 1873-3336
J9 J HAZARD MATER
JI J. Hazard. Mater.
PD APR 5
PY 2016
VL 306
BP 247
EP 256
DI 10.1016/j.jhazmat.2015.12.016
PG 10
WC Engineering, Environmental; Engineering, Civil; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA DK3FV
UT WOS:000374803400027
PM 26745518
ER
PT J
AU Jensen, CD
Corley, DA
Quinn, VP
Doubeni, CA
Zauber, AG
Lee, JK
Zhao, WK
Marks, AR
Schottinger, JE
Ghai, NR
Lee, AT
Contreras, R
Klabunde, CN
Quesenberry, CP
Levin, TR
Mysliwiec, PA
AF Jensen, Christopher D.
Corley, Douglas A.
Quinn, Virginia P.
Doubeni, Chyke A.
Zauber, Ann G.
Lee, Jeffrey K.
Zhao, Wei K.
Marks, Amy R.
Schottinger, Joanne E.
Ghai, Nirupa R.
Lee, Alexander T.
Contreras, Richard
Klabunde, Carrie N.
Quesenberry, Charles P.
Levin, Theodore R.
Mysliwiec, Pauline A.
TI Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual
Screening A Retrospective Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID OCCULT-BLOOD-TEST; COLORECTAL-CANCER MORTALITY;
RANDOMIZED-CLINICAL-TRIAL; COLLEGE-OF-RADIOLOGY; SERVICES TASK-FORCE;
AMERICAN-COLLEGE; ADENOMATOUS POLYPS; QUALITY INDICATORS; JOINT
GUIDELINE; COLONOSCOPY
AB Background: The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown.
Objective: To assess FIT performance characteristics over 4 rounds of annual screening.
Design: Retrospective cohort study.
Setting: Kaiser Permanente Northern and Southern California.
Patients: 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds.
Measurements: Screening participation, FIT positivity (>= 20 mu g of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries.
Results: Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds-7.0% due to a positive FIT result. The FIT positivity rate (5.0%) and positive predictive values (adenoma, 51.5%; CRC, 3.4%) were highest in round 1. Overall, programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% to 78.0% in subsequent rounds.
Limitation: Screening detection, rather than long-term cancer prevention, was evaluated.
Conclusion: Annual FIT screening was associated with high sensitivity for CRC, with high adherence to annual follow-up screening among initial participants. The findings indicate that annual programmatic FIT screening is feasible and effective for population-level CRC screening.
C1 Kaiser Permanente No Calif, Oakland, CA USA.
[Quinn, Virginia P.; Ghai, Nirupa R.; Contreras, Richard] Kaiser Permanente So Calif, Dept Res & Evaluat, 100 South Los Robles,2nd Floor, Pasadena, CA 91101 USA.
[Doubeni, Chyke A.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, 3400 Spruce St,Gate 2, Philadelphia, PA 19104 USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, 485 Lexington Ave,2063A, New York, NY 10017 USA.
[Lee, Jeffrey K.] Univ Calif San Francisco, Div Gastroenterol, 1701 Divisadero St,Suite 120, San Francisco, CA 94115 USA.
[Klabunde, Carrie N.] NIH, Off Dis Prevent, 6100 Execut Blvd,Suite 2B03, Rockville, MD 20852 USA.
[Schottinger, Joanne E.] Kaiser Permanente So Calif, Permanente Med Grp, 393 East Walnut St, Pasadena, CA 91188 USA.
[Lee, Alexander T.] Kaiser Permanente So Calif, Permanente Med Grp, Woodland Hills Med Ctr, 5601 De Soto Ave, Woodland Hills, CA 91365 USA.
[Levin, Theodore R.] Kaiser Permanente Med Ctr, 1425 South Main St, Walnut Creek, CA 94596 USA.
[Mysliwiec, Pauline A.] Permanente Med Grp Inc, 975 Sereno Dr, Vallejo, CA 94589 USA.
RP Corley, DA (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
EM douglas.corley@kp.org
FU National Institutes of Health
FX National Institutes of Health.
NR 33
TC 20
Z9 20
U1 1
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 5
PY 2016
VL 164
IS 7
BP 456
EP +
DI 10.7326/M15-0983
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI6QP
UT WOS:000373625300007
PM 26811150
ER
PT J
AU Taichman, DB
Backus, J
Baethge, C
Bauchner, H
de Leeuw, PW
Drazen, JM
Fletcher, J
Frizelle, FA
Groves, T
Haileamlak, A
James, A
Laine, C
Peiperl, L
Pinborg, A
Sahni, P
AF Taichman, Darren B.
Backus, Joyce
Baethge, Christopher
Bauchner, Howard
de Leeuw, Peter W.
Drazen, Jeffrey M.
Fletcher, John
Frizelle, Frank A.
Groves, Trish
Haileamlak, Abraham
James, Astrid
Laine, Christine
Peiperl, Larry
Pinborg, Anja
Sahni, Peush
TI Sharing Clinical Trial Data: A Proposal From the International Committee
of Medical Journal Editors
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Taichman, Darren B.] ICMJE, Bethesda, MD USA.
[Backus, Joyce] Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA.
[Sahni, Peush] World Assoc Med Editors, New York, NY USA.
RP Taichman, DB (reprint author), Amer Coll Physicians, 190 N Independence Mall West, Philadelphia, PA 19106 USA.
EM dtaichman@acponline.org
OI Groves, Trish/0000-0001-7915-6419
NR 1
TC 13
Z9 13
U1 2
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 5
PY 2016
VL 164
IS 7
BP 505
EP 506
DI 10.7326/M15-2928
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI6QP
UT WOS:000373625300015
PM 26792258
ER
PT J
AU Liang, M
Raley, C
Zheng, X
Kutty, G
Gogineni, E
Sherman, BT
Sun, Q
Chen, XF
Skelly, T
Jones, K
Stephens, R
Zhou, B
Lau, W
Johnson, C
Imamichi, T
Jiang, MK
Dewar, R
Lempicki, RA
Tran, B
Kovacs, JA
Huang, DW
AF Liang, Ma
Raley, Castle
Zheng, Xin
Kutty, Geetha
Gogineni, Emile
Sherman, Brad T.
Sun, Qiang
Chen, Xiongfong
Skelly, Thomas
Jones, Kristine
Stephens, Robert
Zhou, Bin
Lau, William
Johnson, Calvin
Imamichi, Tomozumi
Jiang, Minkang
Dewar, Robin
Lempicki, Richard A.
Tran, Bao
Kovacs, Joseph A.
Huang, Da Wei
TI Distinguishing highly similar gene isoforms with a clustering-based
bioinformatics analysis of PacBio single-molecule long reads
SO BIODATA MINING
LA English
DT Article
DE PacBio; Bioinformatics analysis; Gene isoforms; Repetitive sequences;
Major surface glycoprotein; Pneumocystis; NGS; Uclust
ID SURFACE GLYCOPROTEIN GENES; PNEUMOCYSTIS-CARINII; HUMAN TRANSCRIPTOME;
ANTIGENIC VARIATION; GENOME; COMPLEXITY; CHALLENGES; PATHOGENS;
SEQUENCE; TIME
AB Background: Gene isoforms are commonly found in both prokaryotes and eukaryotes. Since each isoform may perform a specific function in response to changing environmental conditions, studying the dynamics of gene isoforms is important in understanding biological processes and disease conditions. However, genome-wide identification of gene isoforms is technically challenging due to the high degree of sequence identity among isoforms. Traditional targeted sequencing approach, involving Sanger sequencing of plasmid-cloned PCR products, has low throughput and is very tedious and time-consuming. Next-generation sequencing technologies such as Illumina and 454 achieve high throughput but their short read lengths are a critical barrier to accurate assembly of highly similar gene isoforms, and may result in ambiguities and false joining during sequence assembly. More recently, the third generation sequencer represented by the PacBio platform offers sufficient throughput and long reads covering the full length of typical genes, thus providing a potential to reliably profile gene isoforms. However, the PacBio long reads are error-prone and cannot be effectively analyzed by traditional assembly programs.
Results: We present a clustering-based analysis pipeline integrated with PacBio sequencing data for profiling highly similar gene isoforms. This approach was first evaluated in comparison to de novo assembly of 454 reads using a benchmark admixture containing 10 known, cloned msg genes encoding the major surface glycoprotein of Pneumocystis jirovecii. All 10 msg isoforms were successfully reconstructed with the expected length (similar to 1.5 kb) and correct sequence by the new approach, while 454 reads could not be correctly assembled using various assembly programs. When using an additional benchmark admixture containing 22 known P. jirovecii msg isoforms, this approach accurately reconstructed all but 4 these isoforms in their full-length (similar to 3 kb); these 4 isoforms were present in low concentrations in the admixture. Finally, when applied to the original clinical sample from which the 22 known msg isoforms were cloned, this approach successfully identified not only all known isoforms accurately (similar to 3 kb each) but also 48 novel isoforms.
Conclusions: PacBio sequencing integrated with the clustering-based analysis pipeline achieves high-throughput and high-resolution discrimination of highly similar sequences, and can serve as a new approach for genome-wide characterization of gene isoforms and other highly repetitive sequences.
C1 [Liang, Ma; Kutty, Geetha; Gogineni, Emile; Kovacs, Joseph A.] Ctr Clin, Crit Care Med Dept, Frederick, MD USA.
[Raley, Castle; Zheng, Xin; Sherman, Brad T.; Sun, Qiang; Chen, Xiongfong; Skelly, Thomas; Jones, Kristine; Stephens, Robert; Imamichi, Tomozumi; Jiang, Minkang; Dewar, Robin; Lempicki, Richard A.; Tran, Bao; Huang, Da Wei] NIH, Leidos BioMed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Zhou, Bin; Lau, William; Johnson, Calvin] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Huang, Da Wei] NCI, NIH, Bethesda, MD 20892 USA.
RP Huang, DW (reprint author), NIH, Leidos BioMed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM huangdawei@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH Clinical
Center; National Institute of Allergy and Infectious Disease
FX We thank Biswajit Das, Dun Liang, Jun Yang, Xiaoli Jiao, Xiaojun Hu and
Ju Qiu for technical support and discussions throughout the course of
this research. This work was supported by the National Cancer Institute,
National Institutes of Health (Contract HHSN261200800001E); the
Intramural Research Program of the NIH Clinical Center; and the National
Institute of Allergy and Infectious Disease. The contents do not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial products
or organizations imply endorsement by the US Government.
NR 35
TC 1
Z9 1
U1 4
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-0381
J9 BIODATA MIN
JI BioData Min.
PD APR 5
PY 2016
VL 9
AR 13
DI 10.1186/s13040-016-0090-8
PG 13
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DI7FB
UT WOS:000373663600001
PM 27051465
ER
PT J
AU Ordonez-Mena, JM
Schottker, B
Mons, U
Jenab, M
Freisling, H
Bueno-De-Mesquita, B
O'Doherty, MG
Scott, A
Kee, F
Stricker, BH
Hofman, A
de Keyser, CE
Ruiter, R
Soderberg, S
Jousilahti, P
Kuulasmaa, K
Freedman, ND
Wilsgaard, T
de Groot, LCPGM
Kampman, E
Hakansson, N
Orsini, N
Wolk, A
Nilsson, LM
Tjonneland, A
Pajak, A
Malyutina, S
Kubinova, R
Tamosiunas, A
Bobak, M
Katsoulis, M
Orfanos, P
Boffetta, P
Trichopoulou, A
Brenner, H
AF Ordonez-Mena, Jose Manuel
Schoettker, Ben
Mons, Ute
Jenab, Mazda
Freisling, Heinz
Bueno-de-Mesquita, Bas
O'Doherty, Mark G.
Scott, Angela
Kee, Frank
Stricker, Bruno H.
Hofman, Albert
de Keyser, Catherine E.
Ruiter, Rikje
Soderberg, Stefan
Jousilahti, Pekka
Kuulasmaa, Kari
Freedman, Neal D.
Wilsgaard, Tom
de Groot, Lisette C. P. G. M.
Kampman, Ellen
Hakansson, Niclas
Orsini, Nicola
Wolk, Alicja
Nilsson, Lena Maria
Tjonneland, Anne
Pajak, Andrzej
Malyutina, Sofia
Kubinova, Ruzena
Tamosiunas, Abdonas
Bobak, Martin
Katsoulis, Michail
Orfanos, Philippos
Boffetta, Paolo
Trichopoulou, Antonia
Brenner, Hermann
CA Consortium Hlth & Ageing Network C
TI Quantification of the smoking-associated cancer risk with rate
advancement periods: meta-analysis of individual participant data from
cohorts of the CHANCES consortium
SO BMC MEDICINE
LA English
DT Article
DE Smoking; Cancer; Incidence; Mortality; Cohort; Meta-analysis
ID CIGARETTE-SMOKING; BREAST-CANCER; LUNG-CANCER; PROSTATE-CANCER;
EPIDEMIOLOGIC EVIDENCE; MEDITERRANEAN DIET; COLORECTAL-CANCER;
PANCREATIC-CANCER; QUITTING SMOKING; SMOKERS
AB Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.
Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.
Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.
Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
C1 [Ordonez-Mena, Jose Manuel; Schoettker, Ben; Brenner, Hermann] Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
[Ordonez-Mena, Jose Manuel; Schoettker, Ben; Mons, Ute; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
[Jenab, Mazda; Freisling, Heinz] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Chron Dis, Bilthoven, Netherlands.
[Bueno-de-Mesquita, Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Div Epidemiol & Biostat, London, England.
[Bueno-de-Mesquita, Bas] Univ Malaya, Dept Social Prevent Med, Fac Med, Kuala Lumpur, Malaysia.
[O'Doherty, Mark G.; Scott, Angela; Kee, Frank] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland.
[Stricker, Bruno H.; Hofman, Albert; de Keyser, Catherine E.; Ruiter, Rikje] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Soderberg, Stefan] Umea Univ, Dept Publ Hlth & Clin Med, Cardiol & Heart Ctr, Umea, Sweden.
[Jousilahti, Pekka; Kuulasmaa, Kari] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Wilsgaard, Tom] UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway.
[de Groot, Lisette C. P. G. M.; Kampman, Ellen] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands.
[Hakansson, Niclas; Orsini, Nicola; Wolk, Alicja] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Nilsson, Lena Maria] Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Arctic Res Ctr, Umea, Sweden.
[Nilsson, Lena Maria] Umea Univ, Arcum, Arctic Res Ctr, Umea, Sweden.
[Tjonneland, Anne] Danish Canc Soc, Res Ctr, Diet Genes & Environm, Copenhagen, Denmark.
[Pajak, Andrzej] Jagiellonian Univ, Coll Med, Fac Hlth Sci, Krakow, Poland.
[Malyutina, Sofia] Inst Internal & Prevent Med, Novosibirsk, Russia.
[Kubinova, Ruzena] Natl Inst Publ Hlth, Prague, Czech Republic.
[Tamosiunas, Abdonas] Lithuanian Univ Hlth Sci, Inst Cardiol, Kaunas, Lithuania.
[Bobak, Martin] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Katsoulis, Michail; Boffetta, Paolo; Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece.
[Orfanos, Philippos; Trichopoulou, Antonia] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
RP Brenner, H (reprint author), Heidelberg Univ, Network Aging Res, Heidelberg, Germany.; Brenner, H (reprint author), German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 581, D-69120 Heidelberg, Germany.; Brenner, H (reprint author), German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.; Brenner, H (reprint author), German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
EM h.brenner@dkfz.de
RI Brenner, Hermann/B-4627-2017;
OI Brenner, Hermann/0000-0002-6129-1572; Kuulasmaa,
Kari/0000-0003-2165-1411; Ordonez-Mena, Jose Manuel/0000-0002-8965-104X;
Kontto, Jukka/0000-0003-3899-9852
FU FP7 framework program of DG-RESEARCH the European Commission [242244];
Swedish Research Council; Swedish Cancer Foundation; Baden-Wurttemberg
state Ministry of Science, Research and Arts (Stuttgart, Germany);
Federal Ministry of Education and Research (Berlin, Germany); Federal
Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin,
Germany); Hellenic Health Foundation; European Commission (DG SANCO);
Dutch Ministry of Public Health, Welfare and Sports (VWS); National
Institute for Public Health and the Environment (RIVM); Netherlands
Cancer Registry (NKR); Netherlands Organizaton for Health Research and
Development (ZONMW); World Cancer Research Fund (WCRF); Statistics
Netherlands; Health Research Fund (FIS) of the Spanish Ministry of
Health RTICC 'Red Tematica de Investigacion Cooperativa en Cancer
[Rd06/0070/0091, Rd12/0036/0018]; Regional Governments of Andalucia,
Asturias, Basque Country, Murcia [6236]; Navarra, Institute de Salud
Carlos III, Redes de Investigacion Cooperativa [RD06/0020]; Swedish
Cancer Society; Swedish Scientific Council; Regional Government of
Skane; Danish Cancer Society; Welcome Trust [064947, 081081]; US
National Institute on Ageing [R01 AG23522]; Mac Arthur Foundation;
Institut National de la Sante et de la Recherche Medicale (INSERM),
Merck; Sharp & Dohme-Chibret Laboratory; Department of Health and Social
Services; Personal Safety for Northern Ireland; European Union
[HEALTH-F4-2007-201413, 278913]; Intramural Program of the National
Cancer Institute; Erasmus Medical Center; Erasmus University Rotterdam;
Netherlands Organization for Scientific Research; Netherlands
Organization for Health Research and Development; Research Institute for
Diseases in the Elderly; Netherlands Genomics Initiative; Ministry of
'Education Culture, and Science; Ministry of Health, Welfare, and
Sports; European Commission; Municipality of Rotterdam; EU; Norwegian
Research Council; Vasterbotten county Council; Swedish Council for
Working Life and Social Research
FX This work was supported by the FP7 framework program of DG-RESEARCH the
European Commission (Grant no. 242244). The CHANCES project
(www.chancesfp7.eu) is coordinated by the Hellenic Health Foundation,
Greece. The Cohort of Swedish Men (CORM) and the Swedish Mammography
Cohort (SMC) were supported by research grants from the Swedish Research
Council and the Swedish Cancer Foundation. The ESTHER study was funded
by the Baden-Wurttemberg state Ministry of Science, Research and Arts
(Stuttgart, Germany), the Federal Ministry of Education and Research
(Berlin, Germany), and the Federal Ministry of Family Affairs, Senior
Citizens, Women and Youth (Berlin, Germany). The EPIC Greece study was
funded by the Hellenic Health Foundation. The EPIC Netherlands study was
funded by European Commission (DG SANCO), Dutch Ministry of Public
Health, Welfare and Sports (VWS), The National Institute for Public
Health and the Environment (RIVM), the Netherlands Cancer Registry
(NKR), the Netherlands Organizaton for Health Research and Development
(ZONMW), the World Cancer Research Fund (WCRF) and Statistics
Netherlands. The EPIC Spain study was supported by Health Research Fund
(FIS) of the Spanish Ministry of Health RTICC 'Red Tematica de
Investigacion Cooperativa en Cancer (Grant numbers: Rd06/0070/0091 and
Rd12/0036/0018), Regional Governments of Andalucia, Asturias, Basque
Country, Murcia (project 6236) and Navarra, Institute de Salud Carlos
III, Redes de Investigacion Cooperativa (RD06/0020). The EPIC Sweden
study was funded by the Swedish Cancer Society, the Swedish Scientific
Council and the Regional Government of Skane. The EPIC Denmark study was
funded by the Danish Cancer Society. The HAPIEE study was funded by the
Welcome Trust (064947 and 081081), the US National Institute on Ageing
(R01 AG23522), and a grant from Mac Arthur Foundation. MORGAM PRIME was
supported by grants from the Institut National de la Sante et de la
Recherche Medicale (INSERM), Merck, Sharp & Dohme-Chibret Laboratory and
the Department of Health and Social Services and Personal Safety for
Northern Ireland. In addition to the FP7 ftmding for CHANCES, the MORGAM
project received funding from the European Union FP7 projects ENGAGE
(HEALTH-F4-2007-201413) and BiomarCaRE (278913). This supported central
coordination, workshops and part of the activities of the MORGAM Data
Center at THL in Helsinki, Finland. MORGAM Participating Centers are
funded by regional and national governments, research councils,
charities, and other local Socities. The National Institutes of Health
(NIH)-AARP cohort was funded by the Intramural Program of the National
Cancer Institute. The Rotterdam Study (RS) is supported by the Erasmus
Medical Center and Erasmus University Rotterdam; the Netherlands
Organization for Scientific Research; the Netherlands Organization for
Health Research and Development; the Research Institute for Diseases in
the Elderly; the Netherlands Genomics Initiative; the Ministry of
'Education Culture, and Science; the Ministry of Health, Welfare, and
Sports; the European Commission; and the Municipality of Rotterdam. The
SENECA study was funded as a Concerted Action within the EURONUT
programme of the EU. The TROMSO Study was funded by the Norwegian
Research Council and peformed by the University of Tromso in cooperation
the National Health Screening Service. The Vasterbotten Intervention
Program (VIP) was supported by grants from the Vasterbotten county
Council, the Swedish Council for Working Life and Social Research, and
the Swedish Research Council.; The study's funders had no influence on
the design of the study, analysis and interpretation of the data,
writing, review, approval or submission of the manuscript.
NR 42
TC 1
Z9 1
U1 4
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD APR 5
PY 2016
VL 14
AR 62
DI 10.1186/s12916-016-0607-5
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3YY
UT WOS:000373438100001
PM 27044418
ER
PT J
AU Pasquali, SK
Jacobs, JP
Farber, GK
Bertoch, D
Blume, ED
Burns, KM
Campbell, R
Chang, AC
Chung, WK
Riehle-Colarusso, T
Curtis, LH
Forrest, CB
Gaynor, WJ
Gaies, MG
Go, AS
Henchey, P
Martin, GR
Pearson, G
Pemberton, VL
Schwartz, SM
Vincent, R
Kaltman, JR
AF Pasquali, Sara K.
Jacobs, Jeffrey P.
Farber, Gregory K.
Bertoch, David
Blume, Elizabeth D.
Burns, Kristin M.
Campbell, Robert
Chang, Anthony C.
Chung, Wendy K.
Riehle-Colarusso, Tiffany
Curtis, Lesley H.
Forrest, Christopher B.
Gaynor, William J.
Gaies, Michael G.
Go, Alan S.
Henchey, Paul
Martin, Gerard R.
Pearson, Gail
Pemberton, Victoria L.
Schwartz, Steven M.
Vincent, Robert
Kaltman, Jonathan R.
TI Report of the National Heart, Lung, and Blood Institute Working Group An
Integrated Network for Congenital Heart Disease Research
SO CIRCULATION
LA English
DT Article
DE database [publication type]; heart diseases; outcome assessment; health
care
ID LEARNING HEALTH SYSTEM; PEDIATRIC CARDIAC-DISEASE; CLINICAL REGISTRY
DATA; INDIRECT IDENTIFIERS; ADMINISTRATIVE DATA; SURGERY; LINKING;
OUTCOMES; QUALITY; CARE
AB The National Heart, Lung, and Blood Institute convened a working group in January 2015 to explore issues related to an integrated data network for congenital heart disease research. The overall goal was to develop a common vision for how the rapidly increasing volumes of data captured across numerous sources can be managed, integrated, and analyzed to improve care and outcomes. This report summarizes the current landscape of congenital heart disease data, data integration methodologies used across other fields, key considerations for data integration models in congenital heart disease, and the short- and long-term vision and recommendations made by the working group.
C1 [Pasquali, Sara K.; Gaies, Michael G.] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48105 USA.
[Jacobs, Jeffrey P.] Johns Hopkins All Childrens Heart Inst, Dept Surg, St Petersburg, FL USA.
[Farber, Gregory K.] NIMH, NIH, Bethesda, MD 20892 USA.
[Bertoch, David] Childrens Hosp Assoc, Overland Pk, KS USA.
[Blume, Elizabeth D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Burns, Kristin M.; Pearson, Gail; Pemberton, Victoria L.; Kaltman, Jonathan R.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Campbell, Robert; Vincent, Robert] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Chang, Anthony C.] Childrens Hosp Orange Cty, Dept Pediat, Orange, CA 92668 USA.
[Chung, Wendy K.] Columbia Univ, Dept Pediat & Med, New York, NY USA.
[Riehle-Colarusso, Tiffany] Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Atlanta, GA USA.
[Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Forrest, Christopher B.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA.
[Gaynor, William J.] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA USA.
[Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Henchey, Paul] ArborMetrix Inc, Ann Arbor, MI USA.
[Martin, Gerard R.] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Pediat, Washington, DC USA.
[Schwartz, Steven M.] Hosp Sick Children, Dept Crit Care Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Schwartz, Steven M.] Hosp Sick Children, Dept Paediat, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Schwartz, Steven M.] Univ Toronto, Sch Med, Toronto, ON M5S 1A1, Canada.
RP Pasquali, SK (reprint author), Univ Michigan, CS Mott Childrens Hosp, 1540 E Hosp Dr, Ann Arbor, MI 48105 USA.
EM pasquali@med.umich.edu
FU NHLBI
FX This working group was funded by the NHLBI. The views and conclusions
expressed in this report are those of the authors and do not necessarily
represent the official position of the NHLBI, the National Institutes of
Health, or the Centers for Disease Control and Prevention.
NR 40
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Z9 6
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD APR 5
PY 2016
VL 133
IS 14
BP 1410
EP 1418
DI 10.1161/CIRCULATIONAHA.115.019506
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DI1ZE
UT WOS:000373294700009
PM 27045129
ER
PT J
AU Drummond, RA
Lionakis, MS
AF Drummond, Rebecca A.
Lionakis, Michail S.
TI Mechanistic Insights into the Role of C-Type Lectin Receptor/CARD9
Signaling in Human Antifungal Immunity
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Review
DE CARD9; lectins; fungi; Candida; neutrophils; innate immunity
ID PATTERN-RECOGNITION RECEPTOR; CANDIDA-ALBICANS INFECTIONS; INHERITED
CARD9 DEFICIENCY; HOST-DEFENSE; FUNGAL-INFECTION; COMBINED
IMMUNODEFICIENCY; INNATE IMMUNITY; CELL-DIFFERENTIATION; DEEP
DERMATOPHYTOSIS; INDUCED ACTIVATION
AB Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs). CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS). In the last 3 years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2) and CARD9-binding partners (MALT1, BCL10) affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.
C1 [Drummond, Rebecca A.; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lionakism@mail.nih.gov
OI Drummond, Rebecca/0000-0001-5424-7074
FU Intramural Research Program of the National Institutes of Health
(National Institute of Allergy and Infectious Diseases)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Allergy and
Infectious Diseases).
NR 67
TC 3
Z9 3
U1 3
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD APR 5
PY 2016
VL 6
AR 39
DI 10.3389/fcimb.2016.00039
PG 11
WC Immunology; Microbiology
SC Immunology; Microbiology
GA DI3WI
UT WOS:000373430400001
PM 27092298
ER
PT J
AU Thurm, A
Tierney, E
Farmer, C
Albert, P
Joseph, L
Swedo, S
Bianconi, S
Bukelis, I
Wheeler, C
Sarphare, G
Lanham, D
Wassif, CA
Porter, FD
AF Thurm, Audrey
Tierney, Elaine
Farmer, Cristan
Albert, Phebe
Joseph, Lisa
Swedo, Susan
Bianconi, Simona
Bukelis, Irena
Wheeler, Courtney
Sarphare, Geeta
Lanham, Diane
Wassif, Christopher A.
Porter, Forbes D.
TI Development, behavior, and biomarker characterization of
Smith-Lemli-Opitz syndrome: an update
SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS
LA English
DT Article
DE Smith-Lemli-Opitz; Autism; Developmental delay; Sterols
ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE;
CHOLESTEROL-SYNTHESIS; GENETIC SYNDROMES; REDUCTASE GENE; FRAGILE-X;
PHENOTYPE; CHILDREN; PREVALENCE; MUTATIONS
AB Background: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior.
Methods: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants.
Results: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group.
Conclusions: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials.
C1 [Thurm, Audrey; Farmer, Cristan; Albert, Phebe; Joseph, Lisa; Swedo, Susan] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Tierney, Elaine; Bukelis, Irena; Wheeler, Courtney; Sarphare, Geeta; Lanham, Diane] Kennedy Krieger Inst, 716 N Broadway, Baltimore, MD 21205 USA.
[Bianconi, Simona; Wassif, Christopher A.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Bethesda, MD 20892 USA.
[Tierney, Elaine] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
RP Tierney, E (reprint author), Kennedy Krieger Inst, 716 N Broadway, Baltimore, MD 21205 USA.; Tierney, E (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
EM tierney@kennedykrieger.org
FU Intramural Research Program of the National Institute of Mental Health
of the National Institutes of Health [ZIA MH002914]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development, Autism
Speaks; Johns Hopkins Institute for Clinical and Translational Research
(ICTR); National Center for Advancing Translational Sciences (NCATS), a
component of the National Institutes of Health (NIH) [UL1 TR 001079];
NIH Roadmap for Medical Research
FX This work was supported by the Intramural Research Program (ZIA
MH002914) of the National Institute of Mental Health of the National
Institutes of Health and the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, Autism Speaks, and by the Johns
Hopkins Institute for Clinical and Translational Research (ICTR) which
is funded in part by Grant Number UL1 TR 001079 from the National Center
for Advancing Translational Sciences (NCATS), a component of the
National Institutes of Health (NIH), and NIH Roadmap for Medical
Research. Its contents are solely the responsibility of the authors, and
the views expressed in this paper do not necessarily represent the views
of the NIMH, NICHD, NIH, HHS, Johns Hopkins ICTR, NCATS, or the US
Government. We give thanks to the individuals who have SLOS and their
family members who participated in the clinical studies from which this
data is derived.
NR 39
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Z9 2
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1866-1947
EI 1866-1955
J9 J NEURODEV DISORD
JI J. Neurodev. Disord.
PD APR 5
PY 2016
VL 8
AR 12
DI 10.1186/s11689-016-9145-x
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI3VR
UT WOS:000373427900001
PM 27053961
ER
PT J
AU Falcone, EL
Abusleme, L
Swamydas, M
Lionakis, MS
Ding, L
Hsu, AP
Zelazny, AM
Moutsopoulos, NM
Kuhns, DB
Deming, C
Quinones, M
Segre, JA
Bryant, CE
Holland, SM
AF Falcone, E. Liana
Abusleme, Loreto
Swamydas, Muthulekha
Lionakis, Michail S.
Ding, Li
Hsu, Amy P.
Zelazny, Adrian M.
Moutsopoulos, Niki M.
Kuhns, Douglas B.
Deming, Clay
Quinones, Mariam
Segre, Julia A.
Bryant, Clare E.
Holland, Steven M.
TI Colitis susceptibility in p47(phox-/-) mice is mediated by the
microbiome
SO MICROBIOME
LA English
DT Article
DE Chronic granulomatous disease; NADPH; Reactive oxygen species;
p47(phox); Microbiome; Inflammatory bowel disease; Colitis; Dextran
sodium sulfate
ID CHRONIC GRANULOMATOUS-DISEASE; OXIDASE COMPLEX; NADPH OXIDASE; CELLS;
DIFFERENTIATION; IDENTIFICATION; SURVIVAL; BACTERIA; MUCOSA; MUCIN
AB Background: Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored.
Results: Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium.
Conclusions: Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.
C1 [Falcone, E. Liana; Ding, Li; Hsu, Amy P.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Abusleme, Loreto; Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Swamydas, Muthulekha; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Kuhns, Douglas B.] Leidos Biomed Res Inc, Neutrophil Monitoring Lab, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Deming, Clay; Segre, Julia A.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bryant, Clare E.] Univ Cambridge, Dept Vet Med, Madingley Rd, Cambridge, England.
RP Falcone, EL (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM emilia.falcone@nih.gov
OI Falcone, Emilia/0000-0002-5486-1549
FU Division of Intramural Research, the NIAID, NIH; National Cancer
Institute, NIH [HHSN261200800001E]
FX This project was supported by the Division of Intramural Research, the
NIAID, NIH, and in part with federal funds from the National Cancer
Institute, NIH, under Contract No. HHSN261200800001E.
NR 29
TC 2
Z9 2
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2049-2618
J9 MICROBIOME
JI Microbiome
PD APR 5
PY 2016
VL 4
AR 13
DI 10.1186/s40168-016-0159-0
PG 16
WC Microbiology
SC Microbiology
GA DI7IN
UT WOS:000373673000001
PM 27044504
ER
PT J
AU Bane, CE
Ivanov, I
Matafonov, A
Boyd, KL
Cheng, QF
Sherwood, ER
Tucker, EI
Smiley, ST
McCarty, OJT
Gruber, A
Gailani, D
AF Bane, Charles E., Jr.
Ivanov, Ivan
Matafonov, Anton
Boyd, Kelli L.
Cheng, Qiufang
Sherwood, Edward R.
Tucker, Erik I.
Smiley, Stephen T.
McCarty, Owen J. T.
Gruber, Andras
Gailani, David
TI Factor XI Deficiency Alters the Cytokine Response and Activation of
Contact Proteases during Polymicrobial Sepsis in Mice
SO PLOS ONE
LA English
DT Article
ID MOLECULAR-WEIGHT KININOGEN; COAGULATION-FACTOR-XI; FORMATION IN-VIVO;
CECAL LIGATION; BLOOD-COAGULATION; HAGEMAN-FACTOR; HUMAN-PLASMA;
ANTITHROMBOTIC THERAPY; MYOCARDIAL-INFARCTION; LIGHT-CHAIN
AB Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP) suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC) and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/-) mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-alpha and IL-10 and delayed IL-1 beta and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI(-/-)mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI(-/-)animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin) system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.
C1 [Bane, Charles E., Jr.; Ivanov, Ivan; Matafonov, Anton; Boyd, Kelli L.; Cheng, Qiufang; Gailani, David] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Matafonov, Anton] Tomsk Polytech Univ, Dept Bioengn & Organ Chem, Tomsk, Russia.
[Sherwood, Edward R.] Vanderbilt Univ, Dept Anesthesiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Tucker, Erik I.; Gruber, Andras] Aronora Inc, Portland, OR USA.
[Smiley, Stephen T.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[McCarty, Owen J. T.; Gruber, Andras] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA.
RP Gailani, D (reprint author), Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM dave.gailani@vanderbilt.edu
FU National Institutes of Health [HL81326, HL58837, GM116184]
FX The authors wish to acknowledge the support of National Institutes of
Health grants HL81326 and HL58837 (DG) and GM116184 (OJM). DG is a
consultant, and receives consultant's fees from several pharmaceutical
companies. These fees were not used to support the work described in
this manuscript. EIT and AG are employees of the company Aronora.
Aronora provided support in the form of salaries for these individuals,
but did not have any additional role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. The specific roles of these authors are articulated in the
'author contributions' section.
NR 74
TC 3
Z9 3
U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 5
PY 2016
VL 11
IS 4
AR e0152968
DI 10.1371/journal.pone.0152968
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI6HK
UT WOS:000373599600053
PM 27046148
ER
PT J
AU Buck, CB
AF Buck, Christopher B.
TI Exposing the Molecular Machinery of BK Polyomavirus
SO STRUCTURE
LA English
DT Editorial Material
AB BK polyomavirus (BKV) is an opportunistic pathogen that poses a serious threat to organ transplant recipients. In this issue of Structure, Hurdiss and colleagues' (Hurdiss et al., 2016) beautiful new high-resolution cryo-EM reconstruction of BKV provides a structural roadmap for the ongoing development of therapeutic antibodies and vaccines targeting this potentially deadly virus. The study also serves as a platform for exploring the basic biology of virion assembly and infectious entry.
C1 [Buck, Christopher B.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Buck, CB (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM buckc@mail.nih.gov
NR 7
TC 0
Z9 0
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD APR 5
PY 2016
VL 24
IS 4
BP 495
EP 495
DI 10.1016/j.str.2016.03.011
PG 1
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI5VN
UT WOS:000373568700001
PM 27050683
ER
PT J
AU Adams, PD
Aertgeerts, K
Bauer, C
Bell, JA
Berman, HM
Bhat, TN
Blaney, JM
Bolton, E
Bricogne, G
Brown, D
Burley, SK
Case, DA
Clark, KL
Darden, T
Emsley, P
Feher, VA
Feng, ZK
Groom, CR
Harris, SF
Hendle, J
Holder, T
Joachimiak, A
Kleywegt, GJ
Krojer, T
Marcotrigiano, J
Mark, AE
Markley, JL
Miller, M
Minor, W
Montelione, GT
Murshudov, G
Nakagawa, A
Nakamura, H
Nicholls, A
Nicklaus, M
Nolte, RT
Padyana, AK
Peishoff, CE
Pieniazek, S
Read, RJ
Shao, CH
Sheriff, S
Smart, O
Soisson, S
Spurlino, J
Stouch, T
Svobodova, R
Tempel, W
Terwilliger, TC
Tronrud, D
Velankar, S
Ward, SC
Warren, GL
Westbrook, JD
Williams, P
Yang, HW
Young, J
AF Adams, Paul D.
Aertgeerts, Kathleen
Bauer, Cary
Bell, Jeffrey A.
Berman, Helen M.
Bhat, Talapady N.
Blaney, Jeff M.
Bolton, Evan
Bricogne, Gerard
Brown, David
Burley, Stephen K.
Case, David A.
Clark, Kirk L.
Darden, Tom
Emsley, Paul
Feher, Victoria A.
Feng, Zukang
Groom, Colin R.
Harris, Seth F.
Hendle, Jorg
Holder, Thomas
Joachimiak, Andrzej
Kleywegt, Gerard J.
Krojer, Tobias
Marcotrigiano, Joseph
Mark, Alan E.
Markley, John L.
Miller, Matthew
Minor, Wladek
Montelione, Gaetano T.
Murshudov, Garib
Nakagawa, Atsushi
Nakamura, Haruki
Nicholls, Anthony
Nicklaus, Marc
Nolte, Robert T.
Padyana, Anil K.
Peishoff, Catherine E.
Pieniazek, Susan
Read, Randy J.
Shao, Chenghua
Sheriff, Steven
Smart, Oliver
Soisson, Stephen
Spurlino, John
Stouch, Terry
Svobodova, Radka
Tempel, Wolfram
Terwilliger, Thomas C.
Tronrud, Dale
Velankar, Sameer
Ward, Suzanna C.
Warren, Gregory L.
Westbrook, John D.
Williams, Pamela
Yang, Huanwang
Young, Jasmine
TI Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop
SO STRUCTURE
LA English
DT Article
ID PROTEIN DATA-BANK; CAMBRIDGE STRUCTURAL DATABASE; ELECTRON-DENSITY;
TASK-FORCE; INFORMATION; MACROMOLECULES; GENERATION; MOLECULES; TOOLS;
PDB
AB Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, similar to 75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the PDB? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.
C1 [Adams, Paul D.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA.
[Aertgeerts, Kathleen] LLC, DART NeuroSci, San Diego, CA 92131 USA.
[Bauer, Cary] Bruker AXS Inc, Madison, WI 53711 USA.
[Bell, Jeffrey A.; Holder, Thomas] Schrodinger Inc, New York, NY 10036 USA.
[Berman, Helen M.; Burley, Stephen K.; Feng, Zukang; Shao, Chenghua; Westbrook, John D.; Yang, Huanwang; Young, Jasmine] State Univ New Jersey, Ctr Integrat Prote Res, Res Collaboratory Struct Bioinformat Prot D, Piscataway, NJ 08854 USA.
[Berman, Helen M.; Burley, Stephen K.; Feng, Zukang; Marcotrigiano, Joseph; Westbrook, John D.; Yang, Huanwang; Young, Jasmine] State Univ New Jersey, Dept Chem & Chem Biol Rutgers, Piscataway, NJ 08854 USA.
[Bhat, Talapady N.] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA.
[Blaney, Jeff M.; Harris, Seth F.] South San Francisco, Genentech Inc, San Francisco, CA 94080 USA.
[Bolton, Evan] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Bricogne, Gerard] Global Phasing Ltd, Cambridge CB3 0AX, England.
[Brown, David] Charles River Ltd, Struct Biol & Biophys, Cambridge CB10 1XL, England.
[Burley, Stephen K.] Univ Calif San Diego, San Diego Supercomputer Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Clark, Kirk L.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA.
[Darden, Tom] OpenEye Sci, Cambridge, MA 02142 USA.
[Emsley, Paul; Nicholls, Anthony; Warren, Gregory L.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
[Feher, Victoria A.; Murshudov, Garib] Univ Calif San Diego, Dept Chem & Biochem, Drug Design Data Resource, La Jolla, CA 92093 USA.
[Groom, Colin R.] Cambridge Crystallog Data Ctr, Cambridge CB2 1EZ, England.
[Hendle, Jorg; Ward, Suzanna C.] Lilly Biotechnol Ctr, Structural Biol, San Diego, CA 92121 USA.
[Joachimiak, Andrzej] Argonne Natl Lab, Biosci, Structural Biol Ctr, Argonne, IL 60439 USA.
[Kleywegt, Gerard J.] European Bioinformat Inst, European Mol Biol Lab, Protein Data Bank Europe, Cambridge CB10 1SD, England.
[Krojer, Tobias; Velankar, Sameer] Univ Oxford, Structural Genom Consortium, Oxford OX3 7DQ, England.
[Marcotrigiano, Joseph; Montelione, Gaetano T.; Smart, Oliver] State Univ New Jersey, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Mark, Alan E.; Miller, Matthew] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia.
[Markley, John L.] Univ Wisconsin, Dept Biochem, BioMagResBank, Madison, WI 53706 USA.
[Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
[Montelione, Gaetano T.] State Univ New Jersey, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
[Nakagawa, Atsushi; Nakamura, Haruki] Osaka Univ, Inst Prot Res, Protein Data Bank Japan, Osaka 5650871, Japan.
[Nicklaus, Marc] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Computer Aided Drug Design Grp, Frederick, MD 21702 USA.
[Nolte, Robert T.; Peishoff, Catherine E.] Collegeville, GlaxoSmithKline, Collegeville, PA 19426 USA.
[Padyana, Anil K.] Agios Pharmaceut Inc, Cambridge, MA 02139 USA.
[Pieniazek, Susan] Bristol Myers Squibb Res & Dev, Pennington, NJ 08534 USA.
[Read, Randy J.] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
[Soisson, Stephen] Bristol Myers Squibb Res & Dev, Princeton, NJ 08543 USA.
[Soisson, Stephen] Merck Res Labs, West Point, PA 19486 USA.
[Spurlino, John] Janssen Pharmaceut Inc, Spring House, PA 19002 USA.
[Stouch, Terry] Sci Solut LLC, West Windsor, NJ 08550 USA.
[Svobodova, Radka] Masaryk Univ, Natl Ctr Biomol Res, CEITEC Cent European Inst Technol, Brno 62500, Czech Republic.
[Tempel, Wolfram] Univ Toronto, Structural Genom Consortium, Toronto, ON M5G IL7, Canada.
[Terwilliger, Thomas C.] Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA.
[Tronrud, Dale] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA.
[Williams, Pamela] Atex Pharmaceut, Cambridge CB4 0QA, England.
RP Burley, SK (reprint author), State Univ New Jersey, Ctr Integrat Prote Res, Res Collaboratory Struct Bioinformat Prot D, Piscataway, NJ 08854 USA.; Burley, SK (reprint author), State Univ New Jersey, Dept Chem & Chem Biol Rutgers, Piscataway, NJ 08854 USA.; Burley, SK (reprint author), Univ Calif San Diego, San Diego Supercomputer Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.; Feher, VA (reprint author), Univ Calif San Diego, Dept Chem & Biochem, Drug Design Data Resource, La Jolla, CA 92093 USA.; Groom, CR (reprint author), Cambridge Crystallog Data Ctr, Cambridge CB2 1EZ, England.
EM stephen.burley@rcsb.org; vfeher@ucsd.edu; groom@ccdc.cam.ac.uk
RI Svobodova Varekova, Radka/E-2867-2012; Terwilliger, Thomas/K-4109-2012;
Marcotrigiano, Joseph /K-6697-2016; Read, Randy/L-1418-2013; Mark,
Alan/A-8799-2011;
OI Minor, Wladek/0000-0001-7075-7090; Terwilliger,
Thomas/0000-0001-6384-0320; Marcotrigiano, Joseph /0000-0003-0346-3353;
Read, Randy/0000-0001-8273-0047; Mark, Alan/0000-0001-5880-4798; Smart,
Oliver/0000-0002-9669-1998; Kleywegt, Gerard J./0000-0002-4670-0331;
Velankar, Sameer/0000-0002-8439-5964; Nicklaus, Marc/0000-0002-4775-7030
FU National Science Foundation [DBI 1338415]; Wellcome Trust [104948];
JST-NBDC; National Institute of General Medical Sciences [GM109046,
GM111528]
FX The workshop was supported by funding to RCSB PDB by the National
Science Foundation (DBI 1338415); PDBe by the Wellcome Trust (104948);
PDBj by JST-NBDC; BMRB by the National Institute of General Medical
Sciences (GM109046); D3R by the National Institute of General Medical
Sciences (GM111528); registration fees from industrial participants; and
a tax-deductible donation to the wwPDB Foundation by the Bristol-Myers
Squibb Foundation.
NR 38
TC 11
Z9 11
U1 7
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD APR 5
PY 2016
VL 24
IS 4
BP 502
EP 508
DI 10.1016/j.str.2016.02.017
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI5VN
UT WOS:000373568700005
PM 27050687
ER
PT J
AU Fang, ZY
Li, H
Chen, G
Yang, JJ
AF Fang, Zhiyong
Li, Han
Chen, Gang
Yang, JiongJiong
TI Unconscious Processing of Negative Animals and Objects: Role of the
Amygdala Revealed by fMRI
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE category; amygdala; awareness; emotion; context
ID SOCIAL COGNITION; CORTICAL RESPONSES; FEAR-RELEVANT; STIMULI;
PERCEPTION; AWARENESS; EMOTION; PATHWAYS; BRAIN; CONSCIOUSNESS
AB Previous studies have shown that emotional stimuli can be processed through the amygdala without conscious awareness. The amygdala is also involved in processing animate and social information. However, it is unclear whether different categories of pictures (e.g., animals, objects) elicit different activity in the amygdale and other regions without conscious awareness. The objective of this study was to explore whether the factors of category, emotion and picture context modulate brain activation for unconscious processing. Pictures denoting different nonhuman animals and objects in negative and neutral emotional valences were presented using a sandwich-masking paradigm. Half of them were presented with human-related information in the contexts, and half were not. Our results showed significant interaction among category, emotion and context in the amygdala and subcortical regions. Specifically, negative animals elicited stronger activation in these regions than negative objects, especially with human contexts. In addition, there were different correlation patterns between the amygdala and cortical regions according to whether they included human context. There were limited activations in cortical category-related networks. These results suggest that the amygdala and subcortical regions dominantly process negative animals, and contextual information modulates their activities, making threatening stimuli that are most relevant to human survival preferentially processed without conscious awareness.
C1 [Fang, Zhiyong; Li, Han; Yang, JiongJiong] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.
[Fang, Zhiyong; Li, Han; Yang, JiongJiong] Peking Univ, Beijing Lab Behav & Mental Hlth, Beijing 100871, Peoples R China.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Yang, JJ (reprint author), Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.; Yang, JJ (reprint author), Peking Univ, Beijing Lab Behav & Mental Hlth, Beijing 100871, Peoples R China.
EM yangjj@pku.edu.cn
FU Global Research Initiative Program, National Institutes of Health (NIH),
USA [R01TW007897]; National Science Foundation of China [31571114]
FX This research was supported by grants from the Global Research
Initiative Program, National Institutes of Health (NIH), USA
(R01TW007897, JY), and the National Science Foundation of China
(31571114, JY).
NR 62
TC 1
Z9 1
U1 5
U2 14
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD APR 5
PY 2016
VL 10
AR 146
DI 10.3389/fnhum.2016.00146
PG 12
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA DI2PJ
UT WOS:000373338500001
PM 27092067
ER
PT J
AU King, WC
Chen, JY
Belle, SH
Courcoulas, AP
Dakin, GF
Elder, KA
Flum, DR
Hinojosa, MW
Mitchell, JE
Pories, WJ
Wolfe, BM
Yanovski, SZ
AF King, Wendy C.
Chen, Jia-Yuh
Belle, Steven H.
Courcoulas, Anita P.
Dakin, Gregory F.
Elder, Katherine A.
Flum, David R.
Hinojosa, Marcelo W.
Mitchell, James E.
Pories, Walter J.
Wolfe, Bruce M.
Yanovski, Susan Z.
TI Change in Pain and Physical Function Following Bariatric Surgery for
Severe Obesity
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID QUALITY-OF-LIFE; OSTEOARTHRITIS INDEX WOMAC; WESTERN-ONTARIO-UNIVERSITY;
GASTRIC BYPASS-SURGERY; LONGITUDINAL ASSESSMENT; MUSCULOSKELETAL PAIN;
OLDER-ADULTS; WEIGHT-LOSS; LONG-TERM; KNEE OSTEOARTHRITIS
AB IMPORTANCE The variability and durability of improvements in pain and physical function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) are not well described.
OBJECTIVES To report changes in pain and physical function in the first 3 years following bariatric surgery, and to identify factors associated with improvement.
DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study at 10 US hospitals. Adults with severe obesity undergoing bariatric surgery were recruited between February 2005 and February 2009. Research assessments were conducted prior to surgery and annually thereafter. Three-year follow-up through October 2012 is reported.
EXPOSURES Bariatric surgery as clinical care.
MAIN OUTCOMES AND MEASURES Primary outcomes were clinically meaningful presurgery to postsurgery improvements in pain and function using scores from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (ie, improvement of >= 5 points on the norm-based score [range, 0-100]) and 400-meter walk time (ie, improvement of >= 24 seconds) using established thresholds. The secondary outcome was clinically meaningful improvement using the Western Ontario McMaster Osteoarthritis Index (ie, improvement of >= 9.7 pain points and >= 9.3 function points on the transformed score [range, 0-100]).
RESULTS Of 2458 participants, 2221 completed baseline and follow-up assessments (1743 [78.5%] were women; median age was 47 years; median body mass index [BMI] was 45.9; 70.4% underwent RYGB; 25.0% underwent LAGB). At year 1, clinically meaningful improvements were shown in 57.6%(95% CI, 55.3%-59.9%) of participants for bodily pain, 76.5%(95% CI, 74.6%-78.5%) for physical function, and 59.5%(95% CI, 56.4%-62.7%) for walk time. Additionally, among participants with severe knee or disability (633), or hip pain or disability (500) at baseline, approximately three-fourths experienced joint-specific improvements in knee pain (77.1%[95% CI, 73.5%-80.7%]) and in hip function (79.2%[95% CI, 75.3%-83.1%]). Between year 1 and year 3, rates of improvement significantly decreased to 48.6%(95% CI, 46.0%-51.1%) for bodily pain and to 70.2%(95% CI, 67.8%-72.5%) for physical function, but improvement rates for walk time, knee and hip pain, and knee and hip function did not (P for all >=.05). Younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms were associated with presurgery-to-postsurgery improvements in multiple outcomes at years 1, 2, and 3.
CONCLUSIONS AND RELEVANCE Among a cohort of participants with severe obesity undergoing bariatric surgery, a large percentage experienced improvement, compared with baseline, in pain, physical function, and walk time over 3 years, but the percentage with improvement in pain and physical function decreased between year 1 and year 3.
C1 [King, Wendy C.; Chen, Jia-Yuh; Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Courcoulas, Anita P.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15261 USA.
[Dakin, Gregory F.] Weill Cornell Med Ctr, New York, NY USA.
[Elder, Katherine A.; Wolfe, Bruce M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Elder, Katherine A.] Univ Pacific, Forest Grove, OR USA.
[Flum, David R.; Hinojosa, Marcelo W.] Univ Washington, Seattle, WA 98195 USA.
[Mitchell, James E.] Neuropsychiat Res Inst, Fargo, ND USA.
[Pories, Walter J.] E Carolina Univ, Brody Sch Med, Greenville, NC USA.
[Yanovski, Susan Z.] NIDDK, Bethesda, MD 20892 USA.
RP King, WC (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Room 105,130 DeSoto St, Pittsburgh, PA 15261 USA.
EM kingw@edc.pitt.edu
OI King, Wendy/0000-0002-0740-0029
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); Columbia University Medical Center [U01-DK66667]; Cornell
University Medical Center CTRC [UL1-RR024996]; University of Washington
[U01-DK66568]; CTRC [M01RR-00037, UL1-RR024153]; Neuropsychiatric
Research Institute [U01-DK66471]; East Carolina University
[U01-DK66526]; University of Pittsburgh Medical Center [U01-DK66585];
Oregon Health & Science University [U01-DK66555]; [U01 DK066557]
FX LABS-2 was a cooperative agreement funded by the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK). Grant numbers: Data
Coordinating Center-U01 DK066557; Columbia University Medical
Center-U01-DK66667 (in collaboration with Cornell University Medical
Center CTRC, grant UL1-RR024996); University of Washington-U01-DK66568
(in collaboration with CTRC, grant M01RR-00037); Neuropsychiatric
Research Institute-U01-DK66471; East Carolina University-U01-DK66526;
University of Pittsburgh Medical Center-U01-DK66585 (in collaboration
with CTRC, grant UL1-RR024153); Oregon Health & Science
University-U01-DK66555.
NR 40
TC 9
Z9 9
U1 5
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD APR 5
PY 2016
VL 315
IS 13
BP 1362
EP 1371
DI 10.1001/jama.2016.3010
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EP
UT WOS:000373381500020
PM 27046364
ER
PT J
AU Leary, PJ
Tedford, RJ
Bluemke, DA
Bristow, MR
Heckbert, SR
Kawut, SM
Krieger, EV
Lima, JA
Masri, CS
Ralph, DD
Shea, S
Weiss, NS
Kronmal, RA
AF Leary, Peter J.
Tedford, Ryan J.
Bluemke, David A.
Bristow, Michael R.
Heckbert, Susan R.
Kawut, Steven M.
Krieger, Eric V.
Lima, Joao A.
Masri, Carolina S.
Ralph, David D.
Shea, Steven
Weiss, Noel S.
Kronmal, Richard A.
TI Histamine H-2 Receptor Antagonists, Left Ventricular Morphology, and
Heart Failure Risk The MESA Study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiac magnetic resonance imaging; heart failure; prevention
ID PRESERVED EJECTION FRACTION; ATHEROSCLEROSIS RISK; COMMUNITIES;
MEDIATION; FIBROSIS; GEOMETRY; RABBITS; MASS
AB BACKGROUND Myocardial H-2 receptor activation may promote cardiac fibrosis and apoptosis in pre-clinical models and histamine H-2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known.
OBJECTIVES This study sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time.
METHODS We included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging, associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression.
RESULTS H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by cardiac magnetic resonance imaging over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction.
CONCLUSIONS H2RA use was associated with reduced risk for incident HF. Left heart morphology over time suggests less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487) (C) 2016 by the American College of Cardiology Foundation.
C1 [Leary, Peter J.; Krieger, Eric V.; Masri, Carolina S.; Ralph, David D.] Univ Washington, Dept Med, Seattle, WA USA.
[Tedford, Ryan J.; Lima, Joao A.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA.
[Bluemke, David A.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Bristow, Michael R.] Univ Colorado, Dept Med, Aurora, CO USA.
[Heckbert, Susan R.; Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Kawut, Steven M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Dept Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Lima, Joao A.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA.
[Shea, Steven] Columbia Univ, Dept Med, New York, NY USA.
[Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Leary, PJ (reprint author), Univ Washington, Med Ctr, Div Pulm & Crit Care, BB-1361,Campus Box 356522,1959 NE Pacific St, Seattle, WA 98195 USA.
EM learyp@uw.edu
OI Leary, Peter/0000-0001-5716-248X
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR
[UL1-TR-000040, UL1-TR-001079]; National Center For Advancing
Translational Sciences of the National Institutes of Health
[KL2TR000421]
FX This research was supported by contracts N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the
National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040
and UL1-TR-001079 from NCRR. This publication was supported by the
National Center For Advancing Translational Sciences of the National
Institutes of Health under Award KL2TR000421. MESA investigators
reviewed the manuscript for scientific content and consistency of data
interpretation with previous MESA publications. Significant comments
were incorporated before submission for publication. A full list of
participating MESA investigators and institutions can be found at
https://www.mesa-nhlbi.org/aboutMESAPersonnel.aspx. The authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 23
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Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 5
PY 2016
VL 67
IS 13
BP 1544
EP 1552
DI 10.1016/j.jacc.2016.01.045
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DH6ID
UT WOS:000372893300008
PM 27150686
ER
PT J
AU Introne, WJ
Westbroek, W
Cullinane, AR
Groden, CA
Bhambhani, V
Golas, GA
Baker, EH
Lehky, TJ
Snow, J
Ziegler, SG
Adams, DR
Dorward, HM
Hess, RA
Huizing, M
Gahl, WA
Toro, C
AF Introne, Wendy J.
Westbroek, Wendy
Cullinane, Andrew R.
Groden, Catherine A.
Bhambhani, Vikas
Golas, Gretchen A.
Baker, Eva H.
Lehky, Tanya J.
Snow, Joseph
Ziegler, Shira G.
Adams, David R.
Dorward, Heidi M.
Hess, Richard A.
Huizing, Marjan
Gahl, William A.
Toro, Camilo
TI Neurologic involvement in patients with atypical Chediak-Higashi disease
SO NEUROLOGY
LA English
DT Article
ID PARKINSONIAN-SYNDROME; CLINICAL PHENOTYPE; LYST; IDENTIFICATION;
LYSOSOMES; MUTATIONS; GENOTYPE; DOMAIN; CELLS; BEIGE
AB Objective:To delineate the developmental and progressive neurodegenerative features in 9 young adults with the atypical form of Chediak-Higashi disease (CHD) enrolled in a natural history study.Methods:Patients with atypical clinical features, but diagnostically confirmed CHD by standard evaluation of blood smears and molecular genotyping, underwent complete neurologic evaluation, MRI of the brain, electrophysiologic examination, and neuropsychological testing. Fibroblasts were collected to investigate the cellular phenotype and correlation with the clinical presentation.Results:In 9 mildly affected patients with CHD, we documented learning and behavioral difficulties along with developmental structural abnormalities of the cerebellum and posterior fossa, which are apparent early in childhood. A range of progressive neurologic problems emerge in early adulthood, including cerebellar deficits, polyneuropathies, spasticity, cognitive decline, and parkinsonism.Conclusions:Patients with undiagnosed atypical CHD manifesting some of these wide-ranging yet nonspecific neurologic complaints may reside in general and specialty neurology clinics. The absence of the typical bleeding or infectious diathesis in mildly affected patients with CHD renders them difficult to diagnose. Identification of these individuals is important not only for close surveillance of potential CHD-related systemic complications but also for a full understanding of the natural history of CHD and the potential role of the disease-causing protein, LYST, to the pathophysiology of other neurodevelopmental and neurodegenerative disorders.
C1 [Introne, Wendy J.; Groden, Catherine A.; Bhambhani, Vikas; Golas, Gretchen A.; Gahl, William A.; Toro, Camilo] NIH, Off Clin Director, Bldg 10, Bethesda, MD 20892 USA.
[Westbroek, Wendy; Cullinane, Andrew R.; Ziegler, Shira G.; Adams, David R.; Dorward, Heidi M.; Hess, Richard A.; Gahl, William A.] NIH, Human Biochem Genet Sect, Med Genet Branch, Bldg 10, Bethesda, MD 20892 USA.
[Baker, Eva H.] NIH, Natl Human Genome Res Inst, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Lehky, Tanya J.] NIH, Electromyog Sect, Off Clin Director, Natl Inst Neurol Disorders & Stroke, Bldg 10, Bethesda, MD 20892 USA.
[Snow, Joseph] NIH, Off Clin Director, Natl Inst Mental Hlth, Bldg 10, Bethesda, MD 20892 USA.
[Bhambhani, Vikas] Childrens Hosp & Clin Minnesota, Metab & Clin Geneticist, Dept Med Genet, Minneapolis, MN USA.
RP Introne, WJ (reprint author), NIH, Off Clin Director, Bldg 10, Bethesda, MD 20892 USA.
EM wintrone@mail.nih.gov
FU Intramural Research Programs of the National Human Genome Research
Institute; National Institute of Neurological Disorders and Stroke;
Hatfield Clinical Center, NIH, Bethesda, MD
FX Supported by the Intramural Research Programs of the National Human
Genome Research Institute, the National Institute of Neurological
Disorders and Stroke, and the Hatfield Clinical Center, NIH, Bethesda,
MD.
NR 32
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD APR 5
PY 2016
VL 86
IS 14
BP 1320
EP 1328
DI 10.1212/WNL.0000000000002551
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DI1YE
UT WOS:000373292100009
PM 26944273
ER
PT J
AU Little, MP
Wakeford, R
Bouville, A
Simon, SL
AF Little, Mark P.
Wakeford, Richard
Bouville, Andre
Simon, Steven L.
TI Measurement of Fukushima-related radioactive contamination in aquatic
species
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID RADIONUCLIDES; JAPAN
C1 [Little, Mark P.; Bouville, Andre; Simon, Steven L.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA.
[Wakeford, Richard] Univ Manchester, Inst Populat Hlth, Ctr Occupat & Environm Hlth, Manchester M13 9PL, Lancs, England.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA.
EM mark.little@nih.gov
OI Wakeford, Richard/0000-0002-2934-0987
NR 15
TC 0
Z9 0
U1 5
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 5
PY 2016
VL 113
IS 14
BP 3720
EP 3721
DI 10.1073/pnas.1602648113
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI2UI
UT WOS:000373354000030
PM 27035996
ER
PT J
AU Zhu, JJ
Kwan, KM
Mackem, S
AF Zhu, Jianjian
Kwan, Kin Ming
Mackem, Susan
TI Putative oncogene Brachyury (T) is essential to specify cell fate but
dispensable for notochord progenitor proliferation and EMT
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE notochord; Brachyury; cell fate; EMT
ID MESENCHYMAL-LIKE PHENOTYPE; VERTEBRATE DEVELOPMENT; CRE RECOMBINASE;
GENE-FUNCTION; MOUSE; MICE; CHORDOMA; IDENTIFICATION; DUPLICATION;
EXPRESSION
AB The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.
C1 [Zhu, Jianjian; Mackem, Susan] NCI, CDBL, CCR, Frederick, MD 21702 USA.
[Kwan, Kin Ming] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.
RP Mackem, S (reprint author), NCI, CDBL, CCR, Frederick, MD 21702 USA.
EM mackems@mail.nih.gov
FU intramural program of the CCR, NCI
FX We thank CDBL members for discussions and comments on the manuscript;
Richard Behringer for providing the T-KO mice; Hiroshi Sasaki and the
Riken CDB Animal Resources and Genetic Engineering for Foxa2CreER
knock-in mice; Brian Harfe, Bernhard Herrmann, Andrew McMahon, and Mark
Udey for probes and antibody; and Lionel Feigenbaum for generating
transgenic mice. This research was supported by the intramural program
of the CCR, NCI.
NR 40
TC 0
Z9 0
U1 3
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 5
PY 2016
VL 113
IS 14
BP 3820
EP 3825
DI 10.1073/pnas.1601252113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI2UI
UT WOS:000373354000047
PM 27006501
ER
PT J
AU Ray, P
De, S
Mitra, A
Bezstarosti, K
Demmers, JAA
Pfeifer, K
Kassis, JA
AF Ray, Payal
De, Sandip
Mitra, Apratim
Bezstarosti, Karel
Demmers, Jeroen A. A.
Pfeifer, Karl
Kassis, Judith A.
TI Combgap contributes to recruitment of Polycomb group proteins in
Drosophila
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Polycomb; PREs; gene expression; Combgap; PcG recruitment
ID RESPONSE ELEMENTS; HOMEOTIC GENE; DNA-BINDING; TRANSCRIPTIONAL
REGULATION; CUBITUS-INTERRUPTUS; BITHORAX COMPLEX; MELANOGASTER;
CHROMATIN; REPRESSION; PREDICTION
AB Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.
C1 [Ray, Payal; De, Sandip; Mitra, Apratim; Pfeifer, Karl; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Bezstarosti, Karel; Demmers, Jeroen A. A.] Erasmus Univ, Med Ctr, Prote Ctr, NL-3015 GE Rotterdam, Netherlands.
[Bezstarosti, Karel; Demmers, Jeroen A. A.] Erasmus Univ, Med Ctr, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands.
RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM jkassis@mail.nih.gov
OI Kassis, Judith/0000-0001-9268-3213; Pfeifer, Karl/0000-0002-0254-682X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; Netherlands Proteomics Centre
FX We thank Gerard Campbell (University of Pittsburgh) for
cgA22/CyO flies; William Brook (University of Calgary) for
the anti-Cg antibody; Jim Kennison, Hyuck Joon Kang, and Mitzi I. Kuroda
for helpful discussions during the project; Victoria Blake for staining
the discs in Fig. S8B; Lesley Brown, Elissa Lei, Yuzhong Cheng, and
Victoria Blake for comments on this manuscript; and the Bloomington
Stock Center for fly stocks. This work was supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health, and
the Netherlands Proteomics Centre.
NR 49
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U1 4
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 5
PY 2016
VL 113
IS 14
BP 3826
EP 3831
DI 10.1073/pnas.1520926113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI2UI
UT WOS:000373354000048
PM 27001825
ER
PT J
AU Hodson, DJ
Shaffer, AL
Xiao, WM
Wright, GW
Schmitz, R
Phelan, JD
Yang, YD
Webster, DE
Rui, LX
Kohlhammer, H
Nakagawa, M
Waldmann, TA
Staudt, LM
AF Hodson, Daniel J.
Shaffer, Arthur L.
Xiao, Wenming
Wright, George W.
Schmitz, Roland
Phelan, James D.
Yang, Yandan
Webster, Daniel E.
Rui, Lixin
Kohlhammer, Holger
Nakagawa, Masao
Waldmann, Thomas A.
Staudt, Louis M.
TI Regulation of normal B-cell differentiation and malignant B-cell
survival by OCT2
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer biology; lymphoma; germinal center
ID BINDING TRANSCRIPTION FACTORS; OCTAMER DNA MOTIF; OCA-B; COACTIVATOR
OBF-1; UP-REGULATION; IN-VIVO; LYMPHOMA; IMMUNOGLOBULIN; ACTIVATION;
EXPRESSION
AB The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3. Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.
C1 [Hodson, Daniel J.; Shaffer, Arthur L.; Xiao, Wenming; Wright, George W.; Schmitz, Roland; Phelan, James D.; Yang, Yandan; Webster, Daniel E.; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A.; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Hodson, Daniel J.] Univ Cambridge, Dept Haematol, Cambridge CB2 0AH, England.
[Xiao, Wenming] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Kay Kendall Leukaemia Fund Intermediate
Fellowship from the United Kingdom
FX We thank the EUCOMM Consortium for the Pou2f2 ES cells. This research
was supported by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. D.J.H. was supported by a
Kay Kendall Leukaemia Fund Intermediate Fellowship from the United
Kingdom. The views presented in this article do not necessarily reflect
current or future opinion or policy of the US Food and Drug
Administration. Any mention of commercial products is for clarification
and not intended as endorsement.
NR 50
TC 0
Z9 1
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 5
PY 2016
VL 113
IS 14
BP E2039
EP E2046
DI 10.1073/pnas.1600557113
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI2UI
UT WOS:000373354000014
PM 26993806
ER
PT J
AU Huber, BR
Meabon, JS
Hoffer, ZS
Zhang, J
Hoekstra, JG
Pagulayan, KF
McMillan, PJ
Mayer, CL
Banks, WA
Kraemer, BC
Raskind, MA
McGavern, DB
Peskind, ER
Cook, DG
AF Huber, B. R.
Meabon, J. S.
Hoffer, Z. S.
Zhang, J.
Hoekstra, J. G.
Pagulayan, K. F.
McMillan, P. J.
Mayer, C. L.
Banks, W. A.
Kraemer, B. C.
Raskind, M. A.
McGavern, D. B.
Peskind, E. R.
Cook, D. G.
TI BLAST EXPOSURE CAUSES DYNAMIC MICROGLIAL/MACROPHAGE RESPONSES AND
MICRODOMAINS OF BRAIN MICROVESSEL DYSFUNCTION
SO NEUROSCIENCE
LA English
DT Article
DE blood-brain barrier; two-photon microscopy; neuropathology; microglia;
macrophages
ID CHRONIC TRAUMATIC ENCEPHALOPATHY; IN-VIVO; MICROGLIAL ACTIVATION;
WHITE-MATTER; MOUSE MODEL; INJURY; BLOOD; BARRIER; CORTEX; IMPACT
AB Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3 x) blast exposure. Repetitive, but not single, BOPs also caused TNF alpha elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuro-inflammatory responses. Published by Elsevier Ltd. on behalf of IBRO.
C1 [Huber, B. R.] Boston Univ, VA Jamaica Plain, Dept Neurol, Sch Med, Jamaica Plain, MA USA.
[Meabon, J. S.; Pagulayan, K. F.; McMillan, P. J.; Mayer, C. L.; Raskind, M. A.; Peskind, E. R.] VA Puget Sound Healthcare Syst, Northwest Network Mental Illness Res Educ & Clin, Seattle, WA USA.
[Meabon, J. S.; Pagulayan, K. F.; McMillan, P. J.; Mayer, C. L.; Raskind, M. A.; Peskind, E. R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA.
[Hoffer, Z. S.] US Army, Madigan Army Med Ctr, Joint Base Lewis Mcchord, WA USA.
[Zhang, J.; Hoekstra, J. G.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98108 USA.
[Banks, W. A.; Kraemer, B. C.; Cook, D. G.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA.
[Banks, W. A.; Kraemer, B. C.; Cook, D. G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA.
[McGavern, D. B.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Cook, D. G.] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98108 USA.
RP Cook, DG (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, 1660 South Columbian Way, Seattle, WA 98108 USA.
EM dgcook@u.washington.edu
OI Hoekstra, Jake/0000-0001-6597-5878
FU Department of Veterans Affairs Office of Research and Development
Medical Research Service; VA Rehabilitation Research and Development
Service; University of Washington Royalty Research Fund [R01AG046619];
Northwest Network Mental Illness Research, Education and Clinical
Center; Office of Academic Affiliations, Advanced Fellowship Program in
Mental Illness Research and Treatment, Department of Veterans Affairs;
NIH [T32 AG000258]; VA CSR&D Career Development Award [IK2 CX00516]
FX This work was supported by the Department of Veterans Affairs Office of
Research and Development Medical Research Service (D.G.C., B.C.K.), VA
Rehabilitation Research and Development Service (E.R.P.), University of
Washington Royalty Research Fund (D.G.C.); R01AG046619 (W.A.B.);
Northwest Network Mental Illness Research, Education and Clinical Center
(E.R.P., B.R.H., J.S.M., K.F.P., P.J.M., C.L.M.), Office of Academic
Affiliations, Advanced Fellowship Program in Mental Illness Research and
Treatment, Department of Veterans Affairs (B.R.H.); NIH T32 AG000258
(J.S.M.), VA CSR&D Career Development Award Program #IK2 CX00516
(K.F.P.). We thank Dr. Gerard Schellenberg (Univ. Pennsylvania) for
providing Tau knock-out samples.
NR 41
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Z9 2
U1 2
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD APR 5
PY 2016
VL 319
BP 206
EP 220
DI 10.1016/j.neuroscience.2016.01.022
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA DD9RD
UT WOS:000370262400019
PM 26777891
ER
PT J
AU Althoff, KN
Rebeiro, PF
Hanna, DB
Padgett, D
Horberg, MA
Grinsztejn, B
Abraham, AG
Hogg, R
Gill, MJ
Wolff, MJ
Mayor, A
Rachlis, A
Williams, C
Sterling, TR
Kitahata, MM
Buchacz, K
Thorne, JE
Cesar, C
Cordero, FM
Rourke, SB
Sierra-Madero, J
Pape, JW
Cahn, P
McGowan, C
AF Althoff, Keri N.
Rebeiro, Peter F.
Hanna, David B.
Padgett, Denis
Horberg, Michael A.
Grinsztejn, Beatriz
Abraham, Alison G.
Hogg, Robert
Gill, M. John
Wolff, Marcelo J.
Mayor, Angel
Rachlis, Anita
Williams, Carolyn
Sterling, Timothy R.
Kitahata, Mari M.
Buchacz, Kate
Thorne, Jennifer E.
Cesar, Carina
Cordero, Fernando M.
Rourke, Sean B.
Sierra-Madero, Juan
Pape, Jean W.
Cahn, Pedro
McGowan, Catherine
CA na-Accord
Caribbean Cent South Amer Network
TI A picture is worth a thousand words: maps of HIV indicators to inform
research, programs, and policy from NA-ACCORD and CCASAnet clinical
cohorts
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
DE Map; HIV indicators; CD4 T-lymphocyte count; retention in care;
antiretroviral therapy; HIV RNA suppression; North America; Central
America; South America; implementation science
ID ANTIRETROVIRAL THERAPY; INFECTION; CARE; PREVENTION; STATES
AB Introduction: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multicountry maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries.
Methods: Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2 similar to 7% of persons known to be living with HIV in these countries.
Results: Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation similar to 350 cells/mm(3). Haiti, Mexico, and several states had >85% retention in care; lower (50 74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America.
Conclusions: These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.
C1 [Althoff, Keri N.; Abraham, Alison G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Rebeiro, Peter F.; Sterling, Timothy R.; McGowan, Catherine] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Hanna, David B.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Padgett, Denis] Inst Hondureno Seguridad Social, Infect Dis Serv, Dept Internal Med, Tegucigalpa, Honduras.
[Horberg, Michael A.] Kaiser Permanente Mid Atlantic States, Mid Atlantic Permanente Res Inst, Rockville, MD USA.
[Grinsztejn, Beatriz] Fiocruz MS, Evandro Chagas Natl Inst Infect Dis, BR-21045900 Rio De Janeiro, Brazil.
[Hogg, Robert] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Gill, M. John] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Wolff, Marcelo J.] Univ Chile, Fac Med, Dept Med, Santiago 7, Chile.
[Wolff, Marcelo J.] Fdn Arriaran, Santiago, Chile.
[Mayor, Angel] Univ Cent Caribe, Dept Internal Med, Bayamon, PR USA.
[Rachlis, Anita; Thorne, Jennifer E.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON, Canada.
[Williams, Carolyn] NIAID, Epidemiol, Basic Sci Program, Div Aids, Rockville, MD USA.
[Kitahata, Mari M.] Univ Washington, Dept Med, Seattle, WA USA.
[Buchacz, Kate] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Cesar, Carina; Cahn, Pedro] Fdn Huesped, Invest Clin, Buenos Aires, DF, Argentina.
[Cordero, Fernando M.] Univ Peruana Cayetano Heredia, Inst Medicina Trop Alexander von Humboldt, HIV Res Grp, Lima, Peru.
[Rourke, Sean B.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Sierra-Madero, Juan] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infectol, Mexico City, DF, Mexico.
[Pape, Jean W.] Grp Haitien Etud Sarcome Kaposi & Infect Opportun, Port Au Prince, Haiti.
[Pape, Jean W.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
RP Althoff, KN (reprint author), 615 N Wolfe St,Rm E7142, Baltimore, MD 21201 USA.
EM kalthoff@jhu.edu
OI Mayor, Angel M./0000-0002-7705-837X; Rebeiro, Peter/0000-0003-1951-9104;
Hogg, Robert/0000-0003-3463-5488; Justice, Amy/0000-0003-0139-5502
FU National Institutes of Health, USA [P30-AI094189, P30-AI27757,
P30-AI27767, P30-AI036219, P30-AI50410, P30-AI54999, P30-MH62246,
R01-AA16893, R01-CA165937, R01-DA04334, R01-DA11602, R01-DA12568,
R24-AI067039, R56-AI102622, Z01-CP010214, Z01-CP010176]; Center's for
Disease Control and Prevention, USA [CDC200-2006-18797]; Agency for
Healthcare Research and Quality, USA [90047713]; Health Resources and
Services Administration, USA [90051652]; Canadian Institutes of Health
Research, Canada [TGF-96118, HCP-97105, CBR-86906, CBR-94036]; Canadian
Institutes of Health Research (CIHR) New Investigator award; Ontario
Ministry of Health and Long Term Care; Government of Alberta, Canada;
Intramural Research Program of the National Cancer Institute; National
Institutes of Health; [U01-AI69434]; [U01-DA036935]; [U01-HD32632];
[U10-EY08052]; [U10-EY08057]; [U10-EY08067]; [U24-AA020794];
[U54-MD007587]; [UL1-RR024131]; [UL1-TR000083]; [F31-DA037788];
[F31-DA030254]; [G12-MD007583]; [K01-AI071754]; [K01-AI093197];
[K23-EY013707]; [K24-DA00432]; [K24-AI065298]; [KL2-TR000421];
[MO1-RR-00052]; [N02-CP55504]; [P30-AI027763]; [U01-AI069918];
[U01-AA013566]; [U01-AA020790]; [U01-AI31834]; [U01-AI34989];
[U01-AI34993]; [U01-AI34994]; [U01-AI35004]; [U01-AI35039];
[U01-AI35040]; [U01-AI35041]; [U01-AI35042]; [UM1-AI35043];
[U01-AI37613]; [U01-AI37984]; [U01AI38855]; [U01-AI38858];
[U01-AI42590]; [U01-AI68634]; [U01-AI68636]; [U01-AI69432]
FX The NA-ACCORD and collaborating cohorts were supported by grants
U01-AI069918, U01-AA013566, U01-AA020790, U01-AI31834, U01-AI34989,
U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040,
U01-AI35041, U01-AI35042, UM1-AI35043, U01-AI37613, U01-AI37984,
U01AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636,
U01-AI69432, U01-AI69434, U01-DA036935, U01-HD32632, U10-EY08052,
U10-EY08057, U10-EY08067, U24-AA020794, U54-MD007587, UL1-RR024131,
UL1-TR000083, F31-DA037788, F31-DA030254, G12-MD007583, K01-AI071754,
K01-AI093197, K23-EY013707, K24-DA00432, K24-AI065298, KL2-TR000421,
MO1-RR-00052, N02-CP55504, P30-AI027763, P30-AI094189, P30-AI27757,
P30-AI27767, P30-AI036219, P30-AI50410, P30-AI54999, P30-MH62246,
R01-AA16893, R01-CA165937, R01-DA04334, R01-DA11602, R01-DA12568,
R24-AI067039, R56-AI102622, Z01-CP010214, and Z01-CP010176 from the
National Institutes of Health, USA; contract CDC200-2006-18797 from the
Center's for Disease Control and Prevention, USA; contract 90047713 from
the Agency for Healthcare Research and Quality, USA; contract 90051652
from the Health Resources and Services Administration, USA; grants
TGF-96118, HCP-97105, CBR-86906, CBR-94036 from the Canadian Institutes
of Health Research, Canada; Canadian Institutes of Health Research
(CIHR) New Investigator award (A. Burchell); Ontario Ministry of Health
and Long Term Care; and the Government of Alberta, Canada. Additional
support was provided by the Intramural Research Program of the National
Cancer Institute, and National Institutes of Health.
NR 24
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U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD APR 4
PY 2016
VL 19
AR 20707
DI 10.7448/IAS.19.1.20707
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DM2JY
UT WOS:000376174100001
PM 27049052
ER
PT J
AU Herz, DM
Zavala, BA
Bogacz, R
Brown, P
AF Herz, Damian M.
Zavala, Baltazar A.
Bogacz, Rafal
Brown, Peter
TI Neural Correlates of Decision Thresholds in the Human Subthalamic
Nucleus
SO CURRENT BIOLOGY
LA English
DT Article
ID DEEP BRAIN-STIMULATION; BASAL GANGLIA; FRONTAL-CORTEX; MODEL; CONFLICT
AB If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1-9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects' level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects' ability to slow down responses and can induce impulsive suboptimal decisions.
C1 [Herz, Damian M.; Bogacz, Rafal; Brown, Peter] Univ Oxford, MRC, Brain Network Dynam Unit, Mansfield Rd, Oxford OX1 3TH, England.
[Herz, Damian M.; Zavala, Baltazar A.; Bogacz, Rafal; Brown, Peter] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Level 6,West Wing, Oxford OX3 9DU, England.
[Zavala, Baltazar A.] NIH, Surg Neurol Branch, 10 Ctr Dr,3D 20, Bethesda, MD 20814 USA.
RP Brown, P (reprint author), Univ Oxford, MRC, Brain Network Dynam Unit, Mansfield Rd, Oxford OX1 3TH, England.; Brown, P (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Level 6,West Wing, Oxford OX3 9DU, England.
EM peter.brown@ndcn.ox.ac.uk
RI Brown, Peter/J-4307-2016
OI Brown, Peter/0000-0002-5201-3044
FU Medical Research Council [MC_UU_12024/1]; European Union [655605]
FX We would like to thank H. Tan, S. Little, K. Ashkan, M. Hariz, T.
Foltynie, L. Zrinzo, and K. Zaghloul for their contributions to
acquisition and analysis of the primary data and the patients for
volunteering to take part in the study. All patients provided written
informed consent to participate, in accordance with the Declaration of
Helsinki, and the study was approved by the local ethics committee. This
project has received funding from the Medical Research Council (award
MC_UU_12024/1) and the European Union's Horizon 2020 research and
innovation program under Marie Sklodowska-Curie grant agreement 655605.
Original behavioral and electrophysiological data are available on
request.
NR 18
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U1 5
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD APR 4
PY 2016
VL 26
IS 7
BP 916
EP 920
DI 10.1016/j.cub.2016.01.051
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DI1RP
UT WOS:000373273600026
PM 26996501
ER
PT J
AU Storz, G
AF Storz, Gisela
TI New perspectives: Insights into oxidative stress from bacterial studies
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE OxyR; OxyS; MntS
ID OXYR TRANSCRIPTION FACTOR; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM;
HYDROGEN-PEROXIDE; STRUCTURAL BASIS; ACTIVATION; REGULATOR; ENZYMES;
PROTEIN; DAMAGE
AB Studies of the response to hydrogen peroxide as well as the characterization of small, noncoding RNAs and small proteins of less than 50 amino acids in Escherichia coli have given new perspectives on redox sensing, the nature of regulators and gene organization that are relevant to all organisms. Published by Elsevier Inc.
C1 [Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
EM storzg@mail.nih.gov
FU Intramural Research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [ZIA HD001608, ZIA
HD008855]
FX I am thankful for the many interesting and stimulating colleagues such
as Helmut Sies with whom I have had the great pleasure of interacting
over the years. Work carried out in my laboratory was supported by the
Intramural Research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (ZIA HD001608 and ZIA
HD008855).
NR 26
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U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
EI 1096-0384
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD APR 2
PY 2016
VL 595
SI SI
BP 25
EP 27
DI 10.1016/j.abb.2015.11.022
PG 3
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DK1WF
UT WOS:000374705000007
PM 27095210
ER
PT J
AU Eicher, JD
Wakabayashi, Y
Vitseva, O
Esa, N
Yang, YQ
Zhu, J
Freedman, JE
McManus, DD
Johnson, AD
AF Eicher, John D.
Wakabayashi, Yoshiyuki
Vitseva, Olga
Esa, Nada
Yang, Yanqin
Zhu, Jun
Freedman, Jane E.
McManus, David D.
Johnson, Andrew D.
TI Characterization of the platelet transcriptome by RNA sequencing in
patients with acute myocardial infarction
SO PLATELETS
LA English
DT Article
DE RNA-seq; myocardial infarction; platelet aggregation; Gene expression
ID GROWTH IN-VITRO; MESSENGER-RNA; ALPHA-GRANULES; PDGF-C; ACTIVATION;
EXPRESSION; REACTIVITY; COLLAGEN; PROTEIN; VIVO
AB Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited number of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n = 16) vs. non-STEMI (NSTEMI) (n = 16) subtypes. Similar to other studies, we detected 9565 expressed transcripts, including several known platelet-enriched markers (e.g. PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g. wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3, and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions.
C1 [Eicher, John D.; Johnson, Andrew D.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Eicher, John D.; Johnson, Andrew D.] NHLBI, Div Intramural Res, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA.
[Wakabayashi, Yoshiyuki; Yang, Yanqin; Zhu, Jun] NHLBI, Div Intramural Res, DNA Sequencing & Genom Core Lab, Bldg 10, Bethesda, MD 20892 USA.
[Vitseva, Olga] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA.
[Esa, Nada; Freedman, Jane E.; McManus, David D.] Univ Massachusetts, Mem Heart & Vasc Ctr, Worcester, MA 01605 USA.
RP Johnson, AD (reprint author), NHLBI, Populat Sci Branch, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA.
EM johnsonad2@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013
FU University of Massachusetts Medical School [KL2RR031981]; National
Heart, Lung and Blood Institute (NHLBI) [1U01HL105268-01, RFA-HL-12-008]
FX The authors report no declarations of interest. Participant
ascertainment and data collection were supported by University of
Massachusetts Medical School (KL2RR031981) and the National Heart, Lung
and Blood Institute (NHLBI) (1U01HL105268-01, RFA-HL-12-008). Platelet
function and RNA sequencing studies and analysis were supported via the
NHLBI intramural research program.
NR 59
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U1 4
U2 11
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0953-7104
EI 1369-1635
J9 PLATELETS
JI Platelets
PD APR 2
PY 2016
VL 27
IS 3
BP 230
EP 239
DI 10.3109/09537104.2015.1083543
PG 10
WC Cell Biology; Hematology
SC Cell Biology; Hematology
GA DI9VB
UT WOS:000373849700007
PM 26367242
ER
PT J
AU Danis, M
Wilson, Y
White, A
AF Danis, Marion
Wilson, Yolonda
White, Amina
TI Bioethicists Can and Should Contribute to Addressing Racism
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Article
DE inequity; racism; racial violence; health disparities; bioethics;
discrimination
ID HEALTH; DISCRIMINATION; RESILIENCE; FRAMEWORK; DECISION; STRESS; FAMILY;
BIAS; RACE
AB The problems of racism and racially motivated violence in predominantly African American communities in the United States are complex, multifactorial, and historically rooted. While these problems are also deeply morally troubling, bioethicists have not contributed substantially to addressing them. Concern for justice has been one of the core commitments of bioethics. For this and other reasons, bioethicists should contribute to addressing these problems. We consider how bioethicists can offer meaningful contributions to the public discourse, research, teaching, training, policy development, and academic scholarship in response to the alarming and persistent patterns of racism and implicit biases associated with it. To make any useful contribution, bioethicists will require preparation and should expect to play a significant role through collaborative action with others.
C1 [Danis, Marion; White, Amina] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Wilson, Yolonda] Howard Univ, Washington, DC USA.
RP Danis, M (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,RM,1C118, Bethesda, MD 20892 USA.
EM mdanis@nih.gov
FU National Institutes of Health (NIH), Department of Bioethics in the
Clinical Center of the National Institutes of Health
FX The work was supported by the intramural program of the National
Institutes of Health (NIH), particularly the Department of Bioethics in
the Clinical Center of the National Institutes of Health.
NR 50
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U1 1
U2 4
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD APR 2
PY 2016
VL 16
IS 4
BP 3
EP 12
DI 10.1080/15265161.2016.1145283
PG 10
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA DG5CE
UT WOS:000372089500002
PM 26982911
ER
PT J
AU Chen, SC
AF Chen, Stephanie C.
TI Fair Participant Selection: A Negative Obligation Not to Exclude
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
ID CLINICAL-TRIALS
C1 [Chen, Stephanie C.] NIH, Bethesda, MD USA.
RP Chen, SC (reprint author), Natl Inst Hlth Bioeth, Dept Bioeth, 10 Ctr Dr,Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM stephanie.chen2@nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD APR 2
PY 2016
VL 16
IS 4
BP 71
EP 72
DI 10.1080/15265161.2016.1145297
PG 2
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA DG5CE
UT WOS:000372089500026
PM 26982935
ER
PT J
AU Taveira-Dasilva, AM
Moss, J
AF Taveira-Dasilva, Angelo M.
Moss, Joel
TI Epidemiology, pathogenesis and diagnosis of lymphangioleiomyomatosis
SO EXPERT OPINION ON ORPHAN DRUGS
LA English
DT Review
DE Lymphangioleiomyomatosis; Tuberous sclerosis complex (TSC); TSC 1 and
TSC2 mutations; mTOR
ID TUBEROUS SCLEROSIS COMPLEX; GROWTH FACTOR-D; PULMONARY-FUNCTION TESTS;
AIR-FLOW OBSTRUCTION; SERUM VEGF-D; MATRIX METALLOPROTEINASES; TISSUE
INHIBITORS; DIURNAL-VARIATION; LUNG-DISEASES; GENE-PRODUCTS
AB Introduction. Lymphangioleiomyomatosis (LAM) is a disease of women characterized by cystic lung destruction, lymphatic involvement, and renal angiomyolipomas.
Areas covered. LAM is caused by proliferation of abnormal smooth muscle-like LAM cells containing mutations and perhaps epigenetic modifications of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins controlling the mechanistic target of rapamycin (mTOR) signaling pathway. LAM occurs sporadically or in association with tuberous sclerosis complex. LAM may present with dyspnea, recurrent pneumothorax or chylothorax. Pulmonary function tests show reduced flow rates and lung diffusion capacity. Exercise testing may reveal hypoxemia and ventilatory limitation. The severity and progression of disease may be assessed by computer tomography, and pulmonary function and exercise testing. mTOR inhibitors, (e.g., sirolimus) are effective in stabilizing lung function, and reducing the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas.
Expert opinion. Different clinical phenotypes including variable rates of disease progression and variable responses to therapy are seen in LAM patients. No one test is available that predicts the course of disease at the time of diagnosis. Further research regarding the molecular biology of LAM clinical phenotypes is warranted. Recent advances in the characterization of the pathogenesis of LAM are leading to the development of new therapies.
C1 [Taveira-Dasilva, Angelo M.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Taveira-Dasilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU Intermural Research Program, National Heart Lung and Blood Institute of
the NIH [95-H0186]
FX This paper has been supported by the Intermural Research Program,
National Heart Lung and Blood Institute of the NIH, grant number
95-H0186. The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript. This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony, grants or patents received
or pending, or royalties.
NR 98
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Z9 0
U1 2
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 2167-8707
J9 EXPERT OPIN ORPHAN D
JI Exp. Opin. Orphan Drugs
PD APR 2
PY 2016
VL 4
IS 4
BP 369
EP 378
DI 10.1517/21678707.2016.1148597
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG8ND
UT WOS:000372340000001
PM 27833825
ER
PT J
AU Whitehead, SS
AF Whitehead, Stephen S.
TI Development of TV003/TV005, a single dose, highly immunogenic live
attenuated dengue vaccine; what makes this vaccine different from the
Sanofi-Pasteur CYD (TM) vaccine?
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE vaccine infectivity; vaccine attenuation strategies; vaccine
immunogenicity; vaccine efficacy; Dengue; live attenuated dengue vaccine
ID FLAVIVIRUS-NAIVE ADULTS; HEMORRHAGIC-FEVER; VIRUS TYPE-4; TETRAVALENT;
HEALTHY; INFECTIONS; RESPONSES; TRIAL; SAFE; ENHANCEMENT
AB Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYD (TM), a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYD (TM).
C1 [Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM swhitehead@niaid.nih.gov
FU NIH
FX The NIAID research described in this review was supported by the
Intramural Research Program of the NIH. SS Whitehead is a co-inventor of
intellectual property owned by the US Department of Health and Human
Services relating to TV005 and other formulations of the NIAID
tetravalent dengue vaccine. The Laboratory of Infectious Diseases at
NIAID has entered into a collaborative research agreement with Merck for
co-development of the TV005 vaccine. The author has no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed.
NR 27
TC 6
Z9 6
U1 3
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1476-0584
EI 1744-8395
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD APR 2
PY 2016
VL 15
IS 4
SI SI
BP 509
EP 517
DI 10.1586/14760584.2016.1115727
PG 9
WC Immunology
SC Immunology
GA DG6CP
UT WOS:000372170100002
PM 27822982
ER
PT J
AU Hodes, RJ
Buckholtz, N
AF Hodes, Richard J.
Buckholtz, Neil
TI Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD)
Knowledge Portal Aids Alzheimer's Drug Discovery through Open Data
Sharing
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Editorial Material
ID LOCI
C1 [Hodes, Richard J.; Buckholtz, Neil] NIA, NIH, Bethesda, MD 20892 USA.
RP Buckholtz, N (reprint author), NIA, NIH, Bethesda, MD 20892 USA.
EM nbucky11@gmail.com
NR 17
TC 4
Z9 4
U1 1
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1472-8222
EI 1744-7631
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD APR 2
PY 2016
VL 20
IS 4
BP 389
EP 391
DI 10.1517/14728222.2016.1135132
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DE6HQ
UT WOS:000370735000001
PM 26853544
ER
PT J
AU Lee, JS
Romero, R
Han, YM
Kim, HC
Kim, CJ
Hong, JS
Huh, D
AF Lee, Ji Soo
Romero, Roberto
Han, Yu Mi
Kim, Hee Chan
Kim, Chong Jai
Hong, Joon-Seok
Huh, Dongeun
TI Placenta-on-a-chip: a novel platform to study the biology of the human
placenta
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Glucose transfer; microfluidics; organ-on-a-chip; placenta in vitro
model; placental barrier
ID INTRAUTERINE GROWTH RESTRICTION; GESTATIONAL DIABETES-MELLITUS;
COTYLEDON PERFUSION MODEL; AMINO ISOBUTYRIC ACID; IN-VITRO SIMULATION;
LOW-PROTEIN DIET; EX-VIVO; FETAL-GROWTH; LISTERIA-MONOCYTOGENES;
TRYPANOSOMA-CRUZI
AB Objective: Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta.Materials and methods: A Placenta-on-a-Chip microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone.Results: Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations.Conclusion: The Placenta-on-a-Chip microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.
C1 [Lee, Ji Soo] Seoul Natl Univ, Grad Sch, Interdisciplinary Program Bioengn, Seoul, South Korea.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Dept Mol Obstet & Genet, Detroit, MI USA.
[Han, Yu Mi; Hong, Joon-Seok] Seoul Natl Univ, Bundang Hosp, Dept Obstet & Gynecol, 82 Gumi Ro 173 Beon Gil, Songnam 463707, Gyeonggi Do, South Korea.
[Kim, Hee Chan] Seoul Natl Univ, Med Res Ctr, Inst Med & Biol Engn, Seoul, South Korea.
[Kim, Hee Chan] Seoul Natl Univ, Coll Med, Dept Biomed Engn, Seoul, South Korea.
[Kim, Hee Chan] Seoul Natl Univ Hosp, Dept Biomed Engn, Seoul 110744, South Korea.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea.
[Huh, Dongeun] Univ Penn, Dept Bioengn, 240 Skirkanich Hall,210 S 33rd St, Philadelphia, PA 19104 USA.
RP Hong, JS (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Obstet & Gynecol, 82 Gumi Ro 173 Beon Gil, Songnam 463707, Gyeonggi Do, South Korea.; Huh, D (reprint author), Univ Penn, Dept Bioengn, 240 Skirkanich Hall,210 S 33rd St, Philadelphia, PA 19104 USA.; Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov; hjsobgy@gmail.com; huhd@seas.upenn.edu
FU Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH/DHHS; Federal funds
from NICHD, NIH [HSN275201300006C]; Seoul National University Bundang
Hospital Research Fund [03-2013-001]; National Research Foundation of
Korea [2012M3A7B4035286, 2013R1A2A2A04013379]; National Medical Center
and Asan Medical Center in Seoul, Republic of Korea; NIH Director's New
innovator Award [1DP2HL127720-01]; Perinatology Research Branch
FX The authors report no conflicts of interest. This work was supported, in
part, by the Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH/DHHS; and, in part, with Federal funds from
NICHD, NIH under Contract No. HSN275201300006C, and by the Seoul
National University Bundang Hospital Research Fund (Grant No.
03-2013-001) and the National Research Foundation of Korea
(2012M3A7B4035286 and 2013R1A2A2A04013379). We also acknowledge support
from the National Medical Center and Asan Medical Center in Seoul,
Republic of Korea. D. H. is a recipient of the NIH Director's New
innovator Award (1DP2HL127720-01).
NR 100
TC 11
Z9 11
U1 27
U2 103
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD APR 2
PY 2016
VL 29
IS 7
BP 1046
EP 1054
DI 10.3109/14767058.2015.1038518
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DB7QL
UT WOS:000368710600005
PM 26075842
ER
PT J
AU Mhatre, SS
Nagrani, RT
Budukh, A
Chiplunkar, S
Badwe, R
Patil, P
Laversanne, M
Rajaraman, P
Bray, F
Dikshit, R
AF Mhatre, S. S.
Nagrani, R. T.
Budukh, A.
Chiplunkar, S.
Badwe, R.
Patil, P.
Laversanne, M.
Rajaraman, P.
Bray, F.
Dikshit, R.
TI Place of birth and risk of gallbladder cancer in India
SO INDIAN JOURNAL OF CANCER
LA English
DT Article
DE Birth region; gallbladder cancer; population-based cancer registries
AB CONTEXT: Within India, the incidence of gallbladder cancer (GBC) is characterized by marked geographical variation; however, the reasons for these differences are unclear. AIMS: To evaluate the role of place of birth, length of residence, and effect of migration from high-to low-risk region on GBC development. SETTINGS AND DESIGN: Population-based cancer registries (PBCRs); case-control study. SUBJECTS AND METHODS: Data of PBCRs were used to demonstrate geographical variation in GBC incidence rates. A case-control study data examined the role of birth place, residence length, and effect of migration in etiology of GBC. STATISTICAL ANALYSIS: Rate ratios for different PBCRs were estimated using Chennai Cancer Registry as the reference population. Odds ratios (ORs) for developing GBC in a high-risk region compared to a low-risk region and associated 95% confidence interval (CI) were estimated through unconditional logistic regression models using case-control study. RESULTS: GBC shows marked variation in incidence with risk highest in Northeast regions and lowest in South India. OR of 4.82 (95% CI: 3.87-5.99) was observed for developing GBC for individuals born in a high-risk region compared to those born in a low-risk region after adjusting for confounders. A dose-response relationship with increased risk with increased length of residence in a high-risk region was observed (OR lifetime 5.58 [95% CI: 4.42-7.05]; P-trend <= 0.001). The risk persisted even if study participant migrated from high-to low-risk region (OR = 1.36; 95% CI: 1.02-1.82). CONCLUSIONS: The present study signifies the importance of place of birth, length of stay, and effect of migration from high-to low-risk region in the development of GBC. The data indicate role of environmental and genetic factors in etiology of disease.
C1 [Mhatre, S. S.; Nagrani, R. T.; Budukh, A.; Dikshit, R.] Tata Mem Hosp, Ctr Canc Epidemiol, Mumbai, Maharashtra, India.
[Badwe, R.] Tata Mem Hosp, Dept Surg Oncol, Mumbai, Maharashtra, India.
[Patil, P.] Tata Mem Hosp, Dept Digest Dis & Clin Nutr, Mumbai, Maharashtra, India.
[Chiplunkar, S.] Tata Mem Hosp, Adv Ctr Treatment Res & Educ Canc, Chiplunkar Lab, Navi Mumbai, Maharashtra, India.
[Laversanne, M.] Int Agcy Res Canc, Sect Canc Surveillance, Lyon, France.
[Rajaraman, P.] NCI, Ctr Global Hlth, NIH, DHSS, Bethesda, MD 20892 USA.
RP Dikshit, R (reprint author), Tata Mem Hosp, Ctr Canc Epidemiol, Mumbai, Maharashtra, India.
EM dixr24@hotmail.com
OI nagrani, rajini/0000-0002-1708-2319
NR 8
TC 0
Z9 0
U1 0
U2 0
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0019-509X
EI 1998-4774
J9 INDIAN J CANCER
JI Indian J. Cancer
PD APR-JUN
PY 2016
VL 53
IS 2
BP 304
EP 308
DI 10.4103/0019-509X.197723
PG 5
WC Oncology
SC Oncology
GA EJ0XG
UT WOS:000392933700025
PM 28071634
ER
PT J
AU Chaudhary, DV
Patel, DP
Shah, PA
Shah, JV
Sanyal, M
Shrivastav, PS
AF Chaudhary, Darshan V.
Patel, Daxesh P.
Shah, Priyanka A.
Shah, Jaivik V.
Sanyal, Mallika
Shrivastav, Pranav S.
TI Determination of lercanidipine in human plasma by an improved UPLC-MS/MS
method for a bioequivalence study
SO JOURNAL OF PHARMACEUTICAL ANALYSIS
LA English
DT Article
AB An improved and reliable ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of lercanidipine in human plasma. Plasma samples with lercanidipine-d3 as an internal standard (IS) were prepared by solid phase extraction on Phenomenex Strata-X cartridges using 100 mu L of human plasma. Chromatographic analysis was performed on UPLC BEH C-18 (50 mm x 2.1 mm, 1.7 mu m) column under isocratic conditions. Linear calibration curves were obtained over a wide dynamic concentration range of 0.010-20.0 ng/mL. Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. The mean extraction recovery was > 94% for the analyte and IS. Inter-batch and intra-batch precision (% CV) across five quality controls was <5.8%. Bioequivalence study was performed with 36 healthy subjects after oral administration of 10 mg of lercanidipine and the assay reproducibility was evaluated by reanalysis of 133 incurred samples. (C) 2015 Xi'an Jiaotong University. Production and hosting by Elsevier B.V.
C1 [Chaudhary, Darshan V.; Shah, Priyanka A.; Shah, Jaivik V.; Shrivastav, Pranav S.] Gujarat Univ, Sch Sci, Dept Chem, Ahmadabad 380009, Gujarat, India.
[Patel, Daxesh P.] NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
[Sanyal, Mallika] St Xaviers Coll, Dept Chem, Ahmadabad 380009, Gujarat, India.
RP Shrivastav, PS (reprint author), Gujarat Univ, Sch Sci, Dept Chem, Ahmadabad 380009, Gujarat, India.
EM pranav_shrivastav@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2095-1779
EI 2214-0883
J9 J PHARM ANA
JI J. Pharm. Anal.
PD APR
PY 2016
VL 6
IS 2
BP 87
EP 94
DI 10.1016/j.jpha.2015.09.001
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DJ1TQ
UT WOS:000373987600003
ER
PT J
AU Collins, H
Calvo, S
Greenberg, K
Neall, LF
Morrison, S
AF Collins, Heather
Calvo, Sherri
Greenberg, Kathleen
Neall, Lisa Forman
Morrison, Stephanie
TI Information Needs in the Precision Medicine Era: How Genetics Home
Reference Can Help
SO INTERACTIVE JOURNAL OF MEDICAL RESEARCH
LA English
DT Article
DE individualized medicine; patient education as topic; databases; genetic;
health resources
ID GENOMIC MEDICINE; HEALTH; KNOWLEDGE
AB Precision medicine focuses on understanding individual variability in disease prevention, care, and treatment. The Precision Medicine Initiative, launched by President Obama in early 2015, aims to bring this approach to all areas of health care. However, few consumer-friendly resources exist for the public to learn about precision medicine and the conditions that could be affected by this approach to care. Genetics Home Reference, a website from the US National Library of Medicine, seeks to support precision medicine education by providing the public with summaries of genetic conditions and their associated genes, as well as information about issues related to precision medicine such as disease risk and pharmacogenomics. With the advance of precision medicine, consumer-focused resources like Genetics Home Reference can be foundational in providing context for public understanding of the increasing amount of data that will become available.
C1 [Collins, Heather; Greenberg, Kathleen] ICF Int, 9300 Lee Highway, Fairfax, VA 22031 USA.
[Calvo, Sherri; Morrison, Stephanie] NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Neall, Lisa Forman] Med Sci Comp LLC, Rockville, MD USA.
RP Collins, H (reprint author), ICF Int, 9300 Lee Highway, Fairfax, VA 22031 USA.
EM Heather.Collins@icfi.com
NR 25
TC 0
Z9 0
U1 3
U2 3
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1929-073X
J9 INTERACT J MED RES
JI Interact. J. Med. Res.
PD APR-JUN
PY 2016
VL 5
IS 2
BP 94
EP 99
AR e13
DI 10.2196/ijmr.5199
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA ED1PO
UT WOS:000388617600010
PM 27122232
ER
PT J
AU Kozinetz, CA
Royse, K
Graham, SC
Yu, XY
Moye, J
Selwyn, BJ
Forman, MR
Caviness, C
AF Kozinetz, Claudia A.
Royse, Kathryn
Graham, Sarah C.
Yu, Xiaoying
Moye, Jack
Selwyn, Beatrice J.
Forman, Michele R.
Caviness, Chantal
TI Consenting postpartum women for use of routinely collected biospecimens
and/or future biospecimen collection
SO JOURNAL OF COMMUNITY GENETICS
LA English
DT Article
DE Residual; Biospecimen; Postpartum; Consent
ID INFORMED-CONSENT; OPT-IN; SPECIMENS; ATTITUDES; BIOBANKS
AB The National Children's Study (NCS) Harris County, Texas Study Center participated in the NCS Provider Based Sampling (PBS) substudy of the NCS Vanguard Phase pilot. As part of the hospital-based birth cohort component of the PBS substudy, we conducted a secondary data analysis to evaluate the proportion of postpartum women who consented to future biospecimen collection alone and to both future collection and use of residual birth biospecimens. In phase 1, 32 postpartum women at one hospital were asked to consent only to maternal future biospecimen collection. In phase 2, 40 other postpartum women from the same hospital were asked for an additional consent to use residual clinical biospecimens from the birth event that otherwise would be discarded, including cord blood and maternal blood and urine. Among 103 eligible women, a total of 72 participated. They were 28.3 +/- 5.9 years old on average; 58 % were Hispanic; 63 % consented in English, and 37 % in Spanish; 39 % had some college education; 42 % were married; 60 % had an annual family income <$ 30,000; and 51 % were employed. In phase 1, 59 % consented to future biospecimen collection, and in phase 2, 95 % consented to both future collection and use of at least one residual birth biospecimen, with a difference between phases of 36 % [95 % CI 17-54 %]. Demographic characteristics did not differ among those who did and did not consent. Postpartum women were significantly more likely to grant consent for use of future and residual hospital-obtained biospecimens than future biospecimen collection alone.
C1 [Kozinetz, Claudia A.] East Tennessee State Univ, Coll Publ Hlth, Dept Biostat & Epidemiol, Box 70259, Johnson City, TN 37614 USA.
[Royse, Kathryn; Yu, Xiaoying] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Graham, Sarah C.; Caviness, Chantal] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Moye, Jack] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
[Selwyn, Beatrice J.] Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[Forman, Michele R.] Univ Texas Austin, Sch Human Ecol, Dept Nutr Sci, Austin, TX 78712 USA.
RP Kozinetz, CA (reprint author), East Tennessee State Univ, Coll Publ Hlth, Dept Biostat & Epidemiol, Box 70259, Johnson City, TN 37614 USA.
EM kozinetz@etsu.edu
OI Kozinetz, Claudia/0000-0002-3535-0698
FU NICHD NIH HHS [HHSN275200800020C]
NR 16
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1868-310X
EI 1868-6001
J9 J COMMUN GENET
JI J. Commun. Genet.
PD APR
PY 2016
VL 7
IS 2
BP 153
EP 158
DI 10.1007/s12687-016-0261-9
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA EA6ZR
UT WOS:000386778300006
PM 26869364
ER
PT J
AU Fox, CS
Hwang, SJ
Nieto, K
Valentino, M
Mutalik, K
Massaro, JM
Benjamin, EJ
Murabito, JM
AF Fox, Caroline S.
Hwang, Shih-Jen
Nieto, Kenneth
Valentino, Maureen
Mutalik, Karen
Massaro, Joseph M.
Benjamin, Emelia J.
Murabito, Joanne M.
TI Digital Connectedness in the Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular risk; eHealth; epidemiology; mHealth; smartphones;
technology
ID MOBILE HEALTH; EPIDEMIOLOGY; COMMUNITY
AB Background-New avenues of data collection such as eHealth and mobile technology have the potential to revolutionize the way large populations can be assessed and managed outside of standard research and clinical settings.
Methods and Results-A digital connectedness survey was administered within the Framingham Heart Study from 2014 to 2015. The exposure was usage of the Internet, email, cell phones, and smartphones in relation to demographic and cardiovascular disease risk factors; all results were adjusted for age and sex. Among 8096 living study participants, 6503 (80.3%) completed the digital survey. Among survey responders, 5678 (87.4%) reported regular Internet use. Participants reporting regular Internet use were younger (aged 59.1 versus 76.5 years, P<0.0001), were more likely to be employed (70.3% versus 23.7%, P=0.002), and had more favorable cardiovascular disease risk factors than those who did not use the Internet (all P <= 0.05). Overall, 5946 (92.1%) responders reported using cell phones. Among cell phone users, 3907 (67.8%) had smartphones. Smartphone users were younger (aged 55.4 versus 68.5 years, P<0.0001), more likely to be employed (81.1% versus 43.9%, P<0.0001) and to have a college education, and less likely to have hypertension (27.9% versus 55.7%, P=0.0002) than those who did not use smartphones.
Conclusions-Digital connectedness varies substantially by age; connected persons tend to be younger and better educated and to have more favorable cardiovascular disease risk factor profiles. Less than two-thirds of study participants who completed the survey had a smartphone. The generalizability of studies focused on digitally connected persons may have limitations.
C1 [Fox, Caroline S.; Hwang, Shih-Jen] NHLBI, Ctr Populat Studies, NIH, Framingham, MA USA.
[Fox, Caroline S.] Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA USA.
[Nieto, Kenneth; Valentino, Maureen; Mutalik, Karen; Benjamin, Emelia J.; Murabito, Joanne M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiol & Prevent Med, Sch Med, Boston, MA 02215 USA.
[Murabito, Joanne M.] Boston Univ, Dept Med, Gen Internal Med Sect, Sch Med, Boston, MA 02215 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
FU [N01-HC-25195]; [HHSN268201500001I]; [2R01HL092577]; [1R01HL128914];
[1P50HL120163]
FX The National Heart, Lung, and Blood Institute's Framingham Heart Study
is supported by contract N01-HC-25195 and HHSN268201500001I;
2R01HL092577; 1R01HL128914; 1P50HL120163.
NR 17
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD APR
PY 2016
VL 5
IS 4
AR e003193
DI 10.1161/JAHA.116.003193
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DZ1PI
UT WOS:000385609900027
PM 27076568
ER
PT J
AU Morid, MA
Fiszman, M
Raja, K
Jonnalagadda, SR
Del Fiol, G
AF Morid, Mohammad Amin
Fiszman, Marcelo
Raja, Kalpana
Jonnalagadda, Siddhartha R.
Del Fiol, Guilherme
TI Classification of clinically useful sentences in clinical evidence
resources
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Text summarization; Clinical decision support; Natural language
processing; Machine learning
ID BAYESIAN CLASSIFIERS; DENSITY-ESTIMATION; DECISION-SUPPORT; QUESTIONS;
KNOWLEDGE; TEXT; CARE; UPTODATE; SYSTEMS; DOMAIN
AB Most patient care questions raised by clinicians can be answered by online clinical knowledge resources. However, important barriers still challenge the use of these resources at the point of care.
Objective: To design and assess a method for extracting clinically useful sentences from synthesized online clinical resources that represent the most clinically useful information for directly answering clinicians' information needs.
Materials and methods: We developed a Kernel-based Bayesian Network classification model based on different domain-specific feature types extracted from sentences in a gold standard composed of 18 UpToDate documents. These features included UMLS concepts and their semantic groups, semantic predications extracted by SemRep, patient population identified by a pattern-based natural language processing (NLP) algorithm, and cue words extracted by a feature selection technique. Algorithm performance was measured in terms of precision, recall, and F-measure.
Results: The feature-rich approach yielded an F-measure of 74% versus 37% for a feature co-occurrence method (p < 0.001). Excluding predication, population, semantic concept or text-based features reduced the F-measure to 62%, 66%, 58% and 69% respectively (p < 0.01). The classifier applied to Medline sentences reached an F-measure of 73%, which is equivalent to the performance of the classifier on UpToDate sentences (p = 0.62).
Conclusions: The feature-rich approach significantly outperformed general baseline methods. This approach significantly outperformed classifiers based on a single type of feature. Different types of semantic features provided a unique contribution to overall classification performance. The classifier's model and features used for UpToDate generalized well to Medline abstracts. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Morid, Mohammad Amin] Univ Utah, Dept Operat & Informat Syst, David Eccles Sch Business, Salt Lake City, UT USA.
[Fiszman, Marcelo] Natl Lib Med, Lister Hill Ctr, Bethesda, MD USA.
[Raja, Kalpana; Jonnalagadda, Siddhartha R.] Northwestern Univ, Feinberg Sch Med, Div Hlth & Biomed Informat, Dept Prevent Med, Chicago, IL 60611 USA.
[Del Fiol, Guilherme] Univ Utah, Dept Biomed Informat, 421 Wakara Way, Salt Lake City, UT 84108 USA.
RP Del Fiol, G (reprint author), Univ Utah, Dept Biomed Informat, 421 Wakara Way, Salt Lake City, UT 84108 USA.
EM guilherme.delfiol@utah.edu
OI Morid, Mohammad/0000-0002-8818-6545; Del Fiol,
Guilherme/0000-0001-9954-6799
FU National Library of Medicine [1R01LM011416-01, 4R00LM011389-02]
FX This project was supported by Grants 1R01LM011416-01 and 4R00LM011389-02
from the National Library of Medicine.
NR 53
TC 2
Z9 2
U1 4
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD APR
PY 2016
VL 60
BP 14
EP 22
DI 10.1016/j.jbi.2016.01.003
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA DX9HL
UT WOS:000384704100002
PM 26774763
ER
PT J
AU Workman, TE
Fiszman, M
Cairelli, MJ
Nahl, D
Rindflesch, TC
AF Workman, T. Elizabeth
Fiszman, Marcelo
Cairelli, Michael J.
Nahl, Diane
Rindflesch, Thomas C.
TI Spark, an application based on Serendipitous Knowledge Discovery
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Knowledge discovery; Information-seeking behavior; Application
development
ID INFORMATION-RETRIEVAL; BIOMEDICAL TEXT; FRAMEWORK; SEARCH
AB Findings from information-seeking behavior research can inform application development. In this report we provide a system description of Spark, an application based on findings from Serendipitous Knowledge Discovery studies and data structures known as semantic predications. Background information and the previously published IF-SKD model (outlining Serendipitous Knowledge Discovery in online environments) illustrate the potential use of information-seeking behavior in application design. A detailed overview of the Spark system illustrates how methodologies in design and retrieval functionality enable production of semantic predication graphs tailored to evoke Serendipitous Knowledge Discovery in users. (C) 2016 Published by Elsevier Inc.
C1 [Workman, T. Elizabeth; Fiszman, Marcelo; Cairelli, Michael J.; Rindflesch, Thomas C.] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bldg 10, Bethesda, MD 20892 USA.
[Nahl, Diane] Univ Hawaii, Lib & Informat Sci Program, Dept Informat & Comp Sci, Honolulu, HI 96822 USA.
RP Workman, TE (reprint author), NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bldg 10, Bethesda, MD 20892 USA.
EM workmante@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine; National Library of Medicine
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Library of Medicine. This
research was supported in part by an appointment of the first author to
the Lister Hill Center Fellows Program sponsored by the National Library
of Medicine and administered by the Oak Ridge Institute for Science and
Education.
NR 50
TC 0
Z9 0
U1 5
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD APR
PY 2016
VL 60
BP 23
EP 37
DI 10.1016/j.jbi.2015.12.014
PG 15
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA DX9HL
UT WOS:000384704100003
PM 26732995
ER
PT J
AU Hume, S
Aerts, J
Sarnikar, S
Huser, V
AF Hume, Sam
Aerts, Jozef
Sarnikar, Surendra
Huser, Vojtech
TI Current applications and future directions for the CDISC Operational
Data Model standard: A methodological review
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Review
DE ODM; Define-XML; CDISC; Interoperability; Clinical trial; EHR
ID DATA INTERCHANGE STANDARDS; CLINICAL-RESEARCH; SEMANTIC
INTEROPERABILITY; METADATA REGISTRIES; SINGLE-SOURCE; HEALTH-CARE; ODM;
TRIAL; ARCHETYPES; EXCHANGE
AB Introduction: In order to further advance research and development on the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) standard, the existing research must be well understood. This paper presents a methodological review of the ODM literature. Specifically, it develops a classification schema to categorize the ODM literature according to how the standard has been applied within the clinical research data lifecycle. This paper suggests areas for future research and development that address ODM's limitations and capitalize on its strengths to support new trends in clinical research informatics.
Methods: A systematic scan of the following databases was performed: (1) ABI/Inform, (2) ACM Digital, (3) AIS eLibrary, (4) Europe Central PubMed, (5) Google Scholar, (5) IEEE Xplore, (7) PubMed, and (8) ScienceDirect. A Web of Science citation analysis was also performed. The search term used on all databases was "CDISC ODM." The two primary inclusion criteria were: (1) the research must examine the use of ODM as an information system solution component, or (2) the research must critically evaluate ODM against a stated solution usage scenario. Out of 2686 articles identified, 266 were included in a title level review, resulting in 183 articles. An abstract review followed, resulting in 121 remaining articles; and after a full text scan 69 articles met the inclusion criteria.
Results: As the demand for interoperability has increased, ODM has shown remarkable flexibility and has been extended to cover a broad range of data and metadata requirements that reach well beyond ODM's original use cases. This flexibility has yielded research literature that covers a diverse array of topic areas. A classification schema reflecting the use of ODM within the clinical research data lifecycle was created to provide a categorized and consolidated view of the ODM literature. The elements of the framework include: (1) EDC (Electronic Data Capture) and EHR (Electronic Health Record) infrastructure; (2) planning; (3) data collection; (4) data tabulations and analysis; and (5) study archival. The analysis reviews the strengths and limitations of ODM as a solution component within each section of the classification schema. This paper also identifies opportunities for future ODM research and development, including improved mechanisms for semantic alignment with external terminologies, better representation of the CDISC standards used end-to-end across the clinical research data lifecycle, improved support for real-time data exchange, the use of EHRs for research, and the inclusion of a complete study design.
Conclusions: ODM is being used in ways not originally anticipated, and covers a diverse array of use cases across the clinical research data lifecycle. ODM has been used as much as a study metadata standard as it has for data exchange. A significant portion of the literature addresses integrating EHR and clinical research data. The simplicity and readability of ODM has likely contributed to its success and broad implementation as a data and metadata standard. Keeping the core ODM model focused on the most fundamental use cases, while using extensions to handle edge cases, has kept the standard easy for developers to learn and use. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Hume, Sam; Sarnikar, Surendra] Dakota State Univ, Coll Business & Informat Syst, 820 N Washington Ave, Madison, SD 57042 USA.
[Aerts, Jozef] FH Joanneum Univ Appl Sci, Eggenberger Allee 11, A-8020 Graz, Austria.
[Huser, Vojtech] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,Bld 38a,Rm 9N919, Bethesda, MD 20894 USA.
RP Hume, S (reprint author), Dakota State Univ, Coll Business & Informat Syst, 820 N Washington Ave, Madison, SD 57042 USA.
EM swhume@gmail.com; jozef.aerts@fh-joanneum.at; surendra.sarnikar@dsu.edu;
vojtech.huser@nih.gov
OI Hume, Sam/0000-0002-6045-7251
FU Intramural Research Program of the National Institutes of Health
(NIH)/National Library of Medicine (NLM)/Lister Hill National Center for
Biomedical Communications (LHNCBC)
FX This research was supported in part (VH) by the Intramural Research
Program of the National Institutes of Health (NIH)/National Library of
Medicine (NLM)/Lister Hill National Center for Biomedical Communications
(LHNCBC). We wish to thank Wayne Kubick, Rebecca Kush, and Landen Bain
of CDISC, and Sally Cassells of Next Step Clinical Systems for their
insightful comments on a draft version of this work. Sam Hume and Sally
Cassells co-lead the CDISC XML Technologies Team.
NR 101
TC 0
Z9 0
U1 2
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD APR
PY 2016
VL 60
BP 352
EP 362
DI 10.1016/j.jbi.2016.02.016
PG 11
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA DX9HL
UT WOS:000384704100036
PM 26944737
ER
PT J
AU Squiers, L
Brown, D
Parvanta, S
Dolina, S
Kelly, B
Dever, J
Southwell, BG
Sanders, A
Augustson, E
AF Squiers, Linda
Brown, Derick
Parvanta, Sarah
Dolina, Suzanne
Kelly, Bridget
Dever, Jill
Southwell, Brian G.
Sanders, Amy
Augustson, Erik
TI The SmokefreeTXT (SFTXT) Study: Web and Mobile Data Collection to
Evaluate Smoking Cessation for Young Adults
SO JMIR RESEARCH PROTOCOLS
LA English
DT Article
DE tobacco use cessation; text messaging; clinical trial; survey methods;
cell phones; telemedicine
ID RANDOMIZED-TRIAL; PROGRAM
AB Background: Text messaging (short message service, SMS) has been shown to be effective in delivering interventions for various diseases and health conditions, including smoking cessation. While there are many published studies regarding smoking cessation text messaging interventions, most do not provide details about the study's operational methods. As a result, there is a gap in our understanding of how best to design studies of smoking cessation text messaging programs.
Objective: The purpose of this paper is to detail the operational methods used to conduct a randomized trial comparing three different versions of the National Cancer Institute's SmokefreeText (SFTXT) program, designed for smokers 18 to 29 years of age. We detail our methods for recruiting participants from the Internet, reducing fraud, conducting online data collection, and retaining panel study participants.
Methods: Participants were recruited through website advertisements and market research online panels. Screening questions established eligibility for the study (eg, 18 to 29 years of age, current smoker). Antifraud measures screened out participants who could not meet the study requirements. After completing a baseline survey, participants were randomized to one of three study arms, which varied by type and timing of text message delivery. The study offered US $20 gift cards as incentives to complete each of four follow-up surveys. Automated email reminders were sent at designated intervals to increase response rates. Researchers also provided telephone reminders to those who had not completed the survey after multiple email reminders. We calculated participation rates across study arms and compared the final sample characteristics to the Current Population Survey to examine generalizability.
Results: Recruitment methods drove 153,936 unique visitors to the SFTXT Study landing page and 27,360 began the screener. Based on the screening questions, 15,462 out of 27,360 responders (56.51%) were eligible to participate. Of the 15,462 who were eligible, 9486 passed the antifraud measures that were implemented; however, 3882 failed to verify their email addresses or cell phone numbers, leaving 5604 who were invited to complete the baseline survey. Of the 5604 who were invited, 4432 completed the baseline survey, but only 4027 were retained for analysis because 405 did not receive the intervention.
Conclusions: Although antifraud measures helped to catch participants who failed study requirements and could have biased the data collected, it is possible that the email and cell phone verification check excluded some potentially eligible participants from the study. Future research should explore ways to implement verification methods without risking the loss of so many potential participants.
C1 [Squiers, Linda] RTI Int, Ctr Commun Sci, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA.
[Brown, Derick; Parvanta, Sarah; Dolina, Suzanne; Southwell, Brian G.] RTI Int, Res Triangle Pk, NC USA.
[Kelly, Bridget; Dever, Jill] RTI Int, Washington, DC USA.
[Sanders, Amy] ICF Int, Rockville, MD USA.
[Augustson, Erik] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Squiers, L (reprint author), RTI Int, Ctr Commun Sci, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA.
EM lsquiers@rti.org
RI Emchi, Karma/Q-1952-2016
NR 10
TC 0
Z9 0
U1 0
U2 0
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1929-0748
J9 JMIR RES PROTOC
JI JMIR RES. Protoc.
PD APR-JUN
PY 2016
VL 5
IS 2
AR e134
DI 10.2196/resprot.5653
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DT1AH
UT WOS:000381213600056
PM 27349898
ER
PT J
AU Li, M
Kandror, O
Akopian, T
Dharkar, P
Wlodawer, A
Maurizi, MR
Goldberg, AL
AF Li, Mi
Kandror, Olga
Akopian, Tatos
Dharkar, Poorva
Wlodawer, Alexander
Maurizi, Michael R.
Goldberg, Alfred L.
TI Structure and Functional Properties of the Active Form of the
Proteolytic Complex, ClpP1P2, from Mycobacterium tuberculosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ATP-DEPENDENT PROTEASE; COLI CLPAP PROTEASE; ESCHERICHIA-COLI;
CRYSTAL-STRUCTURE; AXIAL CHANNEL; TRANSLOCATION; DEGRADATION; MECHANISM;
PEPTIDE; BINDING
AB The ClpP protease complex and its regulatory ATPases, ClpC1 and ClpX, in Mycobacterium tuberculosis (Mtb) are essential and, therefore, promising drug targets. The Mtb ClpP protease consists of two heptameric rings, one composed of ClpP1 and the other of ClpP2 subunits. Formation of the enzymatically active ClpP1P2 complex requires binding of N-blocked dipeptide activators. We have found a new potent activator, benzoyl-leucine-leucine (Bz-LL), that binds with higher affinity and promotes 3-4-fold higher peptidase activity than previous activators. Bz-LL-activated ClpP1P2 specifically stimulates the ATPase activity of Mtb ClpC1 and ClpX. The ClpC1P1P2 and ClpXP1P2 complexes exhibit 2-3-fold enhanced ATPase activity, peptide cleavage, and ATP-dependent protein degradation. The crystal structure of ClpP1P2 with bound Bz-LL was determined at a resolution of 3.07 angstrom and with benzyloxycarbonyl-Leu-Leu (Z-LL) bound at 2.9 angstrom. Bz-LL was present in all 14 active sites, whereas Z-LL density was not resolved. Surprisingly, Bz-LL adopts opposite orientations in ClpP1 and ClpP2. In ClpP1, Bz-LL binds with the C-terminal leucine side chain in the S1 pocket. One C-terminal oxygen is close to the catalytic serine, whereas the other contacts backbone amides in the oxyanion hole. In ClpP2, Bz-LL binds with the benzoyl group in the S1 pocket, and the peptide hydrogen bonded between parallel beta-strands. The ClpP2 axial loops are extended, forming an open axial channel as has been observed with bound ADEP antibiotics. Thus occupancy of the active sites of ClpP allosterically alters sites on the surfaces thereby affecting the association of ClpP1 and ClpP2 rings, interactions with regulatory ATPases, and entry of protein substrates.
C1 [Li, Mi; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
[Li, Mi] Frederick Natl Lab, Leidos Biomed Res, Basic Res Program, Frederick, MD 21702 USA.
[Kandror, Olga; Akopian, Tatos; Goldberg, Alfred L.] Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
[Dharkar, Poorva; Maurizi, Michael R.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Goldberg, AL (reprint author), Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.; Maurizi, MR (reprint author), NCI, Bldg 37,Rm 2128,37 Convent Dr, Bethesda, MD 20892 USA.
EM mmaurizi@helix.nih.gov; Alfred_Goldberg@hms.harvard.edu
FU United States Department of Energy, Office of Science, Office of Basic
Energy Sciences [W-31-109-Eng-38]
FX Diffraction data were collected on the SER-CAT 22ID beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source was supported by the United States Department of Energy,
Office of Science, Office of Basic Energy Sciences under Contract
W-31-109-Eng-38.
NR 56
TC 3
Z9 3
U1 4
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 1
PY 2016
VL 291
IS 14
BP 7465
EP 7476
DI 10.1074/jbc.M115.700344
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DW2BJ
UT WOS:000383447600022
PM 26858247
ER
PT J
AU Chen, PW
Jian, XY
Heissler, SM
Le, K
Luo, RH
Jenkins, LM
Nagy, A
Moss, J
Sellers, JR
Randazzo, PA
AF Chen, Pei-Wen
Jian, Xiaoying
Heissler, Sarah M.
Le, Kang
Luo, Ruibai
Jenkins, Lisa M.
Nagy, Attila
Moss, Joel
Sellers, James R.
Randazzo, Paul A.
TI The Arf GTPase-activating Protein, ASAP1, Binds Nonmuscle Myosin 2A to
Control Remodeling of the Actomyosin Network
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CIRCULAR DORSAL RUFFLES; ACTIN CYTOSKELETON; CELL-MIGRATION; ANIONIC
PHOSPHOLIPIDS; FOCAL ADHESIONS; PHOSPHORYLATION; DOMAIN; ASSOCIATION;
EXPRESSION; PODOSOMES
AB ASAP1 regulates F-actin-based structures and functions, including focal adhesions (FAs) and circular dorsal ruffles (CDRs), cell spreading and migration. ASAP1 function requires its N-terminal BAR domain. We discovered that nonmuscle myosin 2A (NM2A) directly bound the BAR-PH tandem of ASAP1 in vitro. ASAP1 and NM2A co-immunoprecipitated and colocalized in cells. Knockdown of ASAP1 reduced colocalization of NM2A and F-actin in cells. Knockdown of ASAP1 or NM2A recapitulated each other's effects on FAs, cell migration, cell spreading, and CDRs. The NM2A-interacting BAR domain contributed to ASAP1 control of cell spreading and CDRs. Exogenous expression of NM2A rescued the effect of ASAP1 knockdown on CDRs but ASAP1 did not rescue NM2A knockdown defect in CDRs. Our results support the hypothesis that ASAP1 is a positive regulator of NM2A. Given other binding partners of ASAP1, ASAP1 may directly link signaling and the mechanical machinery of cell migration.
C1 [Chen, Pei-Wen; Jian, Xiaoying; Luo, Ruibai; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
[Jenkins, Lisa M.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Heissler, Sarah M.; Nagy, Attila; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Le, Kang; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Chen, Pei-Wen] Grinnell Coll, Dept Biol, Grinnell, IA 50112 USA.
RP Randazzo, PA (reprint author), NCI, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
FU NCI, National Institutes of Health [BC 007365]; NHLBI, National
Institutes of Health
FX This work was supported by the intramural program of the NCI, National
Institutes of Health (to P. W. C., X. J., R. L., and P. R., Project BC
007365) and NHLBI, National Institutes of Health (to K. L., J. M., A.
N., S. H., and J. S.). The authors declare that they have no conflicts
of interest with the contents of this article.
NR 32
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 1
PY 2016
VL 291
IS 14
BP 7517
EP 7526
DI 10.1074/jbc.M115.701292
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DW2BJ
UT WOS:000383447600026
PM 26893376
ER
PT J
AU Yingling, LR
Brooks, AT
Wallen, GR
Peters-Lawrence, M
McClurkin, M
Cooper-McCann, R
Wiley, KL
Mitchell, V
Saygbe, JN
Johnson, TD
Curry, KE
Johnson, AA
Graham, AP
Graham, LA
Powell-Wiley, TM
AF Yingling, Leah R.
Brooks, Alyssa T.
Wallen, Gwenyth R.
Peters-Lawrence, Marlene
McClurkin, Michael
Cooper-McCann, Rebecca
Wiley, Kenneth L., Jr.
Mitchell, Valerie
Saygbe, Johnetta N.
Johnson, Twanda D.
Curry, Kendrick E.
Johnson, Allan A.
Graham, Avis P.
Graham, Lennox A.
Powell-Wiley, Tiffany M.
TI Community Engagement to Optimize the Use of Web-Based and Wearable
Technology in a Cardiovascular Health and Needs Assessment Study: A
Mixed Methods Approach
SO JMIR MHEALTH AND UHEALTH
LA English
DT Article
DE mHealth; physical activity; community-based participatory research;
obesity; African Americans; activity monitoring; qualitative research;
focus groups; community
ID WEIGHT-LOSS INTERVENTION; AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY;
PARTICIPATORY RESEARCH; PUBLIC-HEALTH; INTERNET; TRACKING; OBESITY;
ADULTS; ENVIRONMENT
AB Background: Resource-limited communities in Washington, D. C. have high rates of obesity-related cardiovascular disease in addition to inadequate physical activity ( PA) facilities and limited Internet access. Engaging community members in the design and implementation of studies to address these health disparities is essential to the success of community-based PA interventions.
Objective: The objective of the study was to use qualitative and quantitative methods to evaluate the feasibility and acceptability of PA-monitoring wristbands and Web-based technology by predominantly African American, church-based populations in resource-limited Washington, D. C. neighborhoods.
Methods: To address cardiovascular health in at-risk populations in Washington, D. C., we joined community leaders to establish a community advisory board, the D. C. Cardiovascular Health and Obesity Collaborative ( D. C. CHOC). As their first initiative, the Washington, D. C. Cardiovascular Health and Needs Assessment intends to evaluate cardiovascular health, social determinants of health, and PA-monitoring technologies. At the recommendation of D. C. CHOC members, we conducted a focus group and piloted the proposed PA-monitoring system with community members representing churches that would be targeted by the Cardiovascular Health and Needs Assessment. Participants ( n= 8) agreed to wear a PA-monitoring wristband for two weeks and to log cardiovascular health factors on a secure Internet account. Wristbands collected accelerometer-based data that participants uploaded to a wireless hub at their church. Participants agreed to return after two weeks to participate in a moderated focus group to share experiences using this technology. Feasibility was measured by Internet account usage, wristband utilization, and objective PA data. Acceptability was evaluated through thematic analysis of verbatim focus group transcripts.
Results: Study participants ( 5 males, 3 females) were African American and age 28-70 years. Participant wristbands recorded data on 10.1+/-1.6 days. Two participants logged cardiovascular health factors on the website. Focus group transcripts revealed that participants felt positively about incorporating the device into their church-based populations, given improvements were made to device training, hub accessibility, and device feedback.
Conclusions: PA-monitoring wristbands for objectively measuring PA appear to be a feasible and acceptable technology in Washington, D. C., resource-limited communities. User preferences include immediate device feedback, hands-on device training, explicit instructions, improved central hub accessibility, and designation of a church member as a trained point-of-contact. When implementing technology-based interventions in resource-limited communities, engaging the targeted community may aid in early identification of issues, suggestions, and preferences.
C1 [Yingling, Leah R.; McClurkin, Michael; Mitchell, Valerie; Saygbe, Johnetta N.; Powell-Wiley, Tiffany M.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,5-3330 10 Ctr Dr, Bethesda, MD 20892 USA.
[Brooks, Alyssa T.; Wallen, Gwenyth R.; Cooper-McCann, Rebecca; Johnson, Twanda D.] NIH, Clin Ctr, Bethesda, MD USA.
[Peters-Lawrence, Marlene] NHLBI, Off Clin Director, Div Intramural Res, NIH, Bethesda, MD USA.
[Wiley, Kenneth L., Jr.] NHGRI, Div Genom Med, NIH, Bethesda, MD USA.
[Curry, Kendrick E.] Penn Ave Baptist Church, Washington, DC USA.
[Johnson, Allan A.; Graham, Avis P.; Graham, Lennox A.] Howard Univ, Coll Nursing & Allied Hlth Sci, Washington, DC USA.
RP Powell-Wiley, TM (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,5-3330 10 Ctr Dr, Bethesda, MD 20892 USA.
EM tiffany.powell@nih.gov
OI Yingling, Leah/0000-0002-7851-690X
FU NHGRI NIH HHS [HHSN268201400023C]
NR 47
TC 1
Z9 1
U1 10
U2 10
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 2291-5222
J9 JMIR MHEALTH UHEALTH
JI JMIR mHealth uHealth
PD APR-JUN
PY 2016
VL 4
IS 2
BP 38
EP 55
AR e38
DI 10.2196/mhealth.4489
PG 18
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DT0OH
UT WOS:000381182400004
PM 27113680
ER
PT J
AU Taber, JM
Klein, WMP
Ferrer, RA
Augustson, E
Patrick, H
AF Taber, Jennifer M.
Klein, William M. P.
Ferrer, Rebecca A.
Augustson, Erik
Patrick, Heather
TI A Pilot Test of Self-Affirmations to Promote Smoking Cessation in a
National Smoking Cessation Text Messaging Program
SO JMIR MHEALTH AND UHEALTH
LA English
DT Article
DE self-affirmation; smoking cessation; mHealth; text messaging;
theoretical study; self concept; motivation
ID SOCIAL-PSYCHOLOGICAL INTERVENTION; HEALTH-RISK INFORMATION; ACHIEVEMENT
GAP; BEHAVIOR-CHANGE; METAANALYSIS; SMOKERS; DEFENSIVENESS; TRIAL
AB Background: Although effective smoking cessation treatments, including mHealth interventions, have been empirically validated and are widely available, smoking relapse is likely. Self-affirmation, a process through which individuals focus on their strengths and behaviors, has been shown to reduce negative effects of self-threats and to promote engagement in healthier behavior.
Objective: To assess the feasibility of incorporating self-affirmations into an existing text messaging-based smoking cessation program ( Smokefree TXT) and to determine whether self-affirmation led to greater engagement and higher cessation rates than the standard intervention.
Methods: Data were collected from smokers ( n= 1261) who subscribed to a free smoking cessation program and met eligibility criteria. The intervention lasted 42 days. The original design was a 2 ( Baseline affirmation: 5-item questionnaire present vs absent) x 2 ( Integrated affirmation: texts present vs absent) factorial design. Only 17 eligible users completed all baseline affirmation questions and these conditions did not influence any outcomes, so we collapsed across baseline affirmation conditions in analysis. In the integrated affirmation conditions, affirmations replaced approximately 20% of texts delivering motivational content.
Results: In all, 687 users remained enrolled throughout the 42-day intervention and 81 reported smoking status at day 42. Among initiators ( n= 1261), self-affirmation did not significantly improve ( 1) intervention completion, ( 2) days enrolled, ( 3) 1-week smoking status, or ( 4) 6-week smoking status ( all Ps>.10); and among the 687 completers, there were no significant effects of affirmation on cessation ( Ps>.25). However, among the 81 responders, those who received affirmations were more likely to report cessation at 6 weeks ( 97.5%; 39 of 40) than those not given affirmations ( 78.1%; 32 of 41;.2( 1)= 7.08, P=. 008).
Conclusion: This proof-of-concept study provides preliminary evidence that self-affirmation can be integrated into existing text-based cessation programs, as the affirmations did not lead to any adverse effects ( ie, less engagement or lower rates of cessation). Among those who reported smoking status at the end of the intervention period ( 6.4% of eligible respondents), affirmations facilitated cessation. This study provides a "proof-of-concept" that brief, low-touch interventions may be integrated into a text messaging program with potential benefits, minimal disruption to the program or users, and little cost. Many questions remain regarding how self-affirmation and similar approaches can promote engagement in population interventions.
C1 [Taber, Jennifer M.; Klein, William M. P.; Augustson, Erik] NCI, Behav Res Program, NIH, Rockville, MD USA.
[Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, NIH, Rockville, MD USA.
[Patrick, Heather] Envolve PeopleCare, Appl Behav Change Sci, Bethesda, MD USA.
RP Taber, JM (reprint author), Kent State Univ, Dept Psychol Sci, 309 Kent Hall Annex, Kent, OH 44242 USA.
EM jtaber1@kent.edu
NR 18
TC 0
Z9 0
U1 3
U2 3
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 2291-5222
J9 JMIR MHEALTH UHEALTH
JI JMIR mHealth uHealth
PD APR-JUN
PY 2016
VL 4
IS 2
BP 373
EP 378
AR e71
DI 10.2196/mhealth.5635
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DT0OH
UT WOS:000381182400029
PM 27278108
ER
PT J
AU Wheelock, KM
Sinha, M
Knowler, WC
Nelson, RG
Fufaa, GD
Hanson, RL
AF Wheelock, Kevin M.
Sinha, Madhumita
Knowler, William C.
Nelson, Robert G.
Fufaa, Gudeta D.
Hanson, Robert L.
TI Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian
Children
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BODY-MASS INDEX; PIMA-INDIANS; INSULIN-RESISTANCE; CARDIOVASCULAR RISK;
MELLITUS; OBESITY; CHILDHOOD; ADOLESCENTS; PREVALENCE; PREDICTORS
AB Context: Data are lacking on how metabolic risk factors during childhood affect the long-term risk of type 2 diabetes.
Objectives: Assess four metabolic risk factors as predictors of type 2 diabetes and determine whether the risk differs between younger and older children.
Design: In a prospective cohort study conducted between 1965 and 2007, participants were followed for development of diabetes. Baseline measurements included body mass index (BMI), blood pressure, serum cholesterol, and 2-hour plasma glucose after an oral glucose tolerance test. Additional analyses divided subjects into two groups according to baseline age, 5-11 and 12-19 years.
Setting: Gila River Indian Community in Arizona.
Participants: A total of 5532 nondiabetic Pima Indian children 5-19 years old.
Results: A total of 1281 children developed diabetes (median follow-up, 12.4 years). Diabetes incidence was higher in overweight children (BMI >= 85th percentile) than in nonoverweight children. Nonoverweight children had the lowest risk of diabetes (20-year cumulative incidence, 9.5%), whereas overweight children with impaired glucose tolerance (2-hour glucose >= 140 mg/dL) had the highest (79.0%). The relative risk for children with metabolic abnormalities compared with their healthy counterparts was higher in younger children than in older children early in follow-up. BMI and 2-hour glucose were related to incident diabetes in multivariable models (predicted 15-year cumulative incidence for the highest vs lowest quartile was 3.9 and 1.8 times as high for BMI and 2-hour glucose, respectively; P < .001), whereas blood pressure and cholesterol were not.
Conclusions: BMI and impaired glucose tolerance in children are strong predictors of type 2 diabetes. Other components of the "metabolic syndrome" are not.
C1 [Wheelock, Kevin M.; Sinha, Madhumita; Knowler, William C.; Nelson, Robert G.; Fufaa, Gudeta D.; Hanson, Robert L.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA.
RP Sinha, M (reprint author), NIDDK, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM madhumita.Sinha@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases. Part
of this work was presented at the American Diabetes Association 75th
Scientific Sessions, June 5-9, 2015, Boston, MA.
NR 34
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1437
EP 1444
DI 10.1210/jc.2015-4309
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400016
PM 26913636
ER
PT J
AU Aroda, VR
Edelstein, SL
Goldberg, RB
Knowler, WC
Marcovina, SM
Orchard, TJ
Bray, GA
Schade, DS
Temprosa, MG
White, NH
Crandall, JP
AF Aroda, Vanita R.
Edelstein, Sharon L.
Goldberg, Ronald B.
Knowler, William C.
Marcovina, Santica M.
Orchard, Trevor J.
Bray, George A.
Schade, David S.
Temprosa, Marinella G.
White, Neil H.
Crandall, Jill P.
CA Diabet Prevention Program Res Grp
TI Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes
Prevention Program Outcomes Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; PLACEBO-CONTROLLED TRIAL; THERAPY;
HOMOCYSTEINE; ASSOCIATION; NEUROPATHY; ABSORPTION; BIGUANIDES;
DIAGNOSIS; COBALAMIN
AB Context: Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.
Objective: To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS).
Design: Secondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years.
Setting: Twenty-seven study centers in the United States.
Patients: DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and over-weight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively. Interventions: Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS).
Main Outcome Measures: B12 deficiency, anemia, and peripheral neuropathy.
Results: Low B12 (<= 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs5.4%; P = .12). Combined low and borderline-low B12(<= 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use, 1.13; 95% confidence interval, 1.06-1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels.
Conclusions: Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.
C1 [Aroda, Vanita R.] MedStar Hlth Res Inst, Hyattsville, MD 20782 USA.
[Edelstein, Sharon L.; Temprosa, Marinella G.] George Washington Univ, Rockville, MD 20852 USA.
[Goldberg, Ronald B.] Univ Miami, Miami, FL 33146 USA.
[Knowler, William C.] NIDDK, Phoenix, AZ 85014 USA.
[Marcovina, Santica M.] Univ Washington, Seattle, WA 98185 USA.
[Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Bray, George A.] Pennington Biomed Res Inst, Baton Rouge, LA 70808 USA.
[Schade, David S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[White, Neil H.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10461 USA.
RP Crandall, JP (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM dppmail@bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Intramural Research
Program; Indian Health Service; National Institute of Child Health and
Human Development; National Institute on Aging; Office of Research on
Women's Health; National Center for Minority Health and Human Disease;
Centers for Disease Control and Prevention; American Diabetes
Association; Bristol-Myers Squibb; Parke-Davis; National Eye Institute;
National Heart, Lung, and Blood Institute
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health is the primary funding
agency for this study.; During the DPP and DPPOS, the NIDDK provided
funding to the clinical centers and the Coordinating Center for the
design and conduct of the study, and the collection, management,
analysis, and interpretation of the data. The Southwestern American
Indian Centers were supported directly by the NIDDK, including its
Intramural Research Program, and the Indian Health Service. The General
Clinical Research Center Program, National Center for Research
Resources, and the Department of Veterans Affairs supported data
collection at many of the clinical centers. Funding was also provided by
the National Institute of Child Health and Human Development, the
National Institute on Aging, the National Eye Institute, the National
Heart, Lung, and Blood Institute, the Office of Research on Women's
Health, the National Center for Minority Health and Human Disease, the
Centers for Disease Control and Prevention, and the American Diabetes
Association. Bristol-Myers Squibb and Parke-Davis provided additional
funding and material support during the DPP, Lipha (Merck-Sante)
provided medication, and LifeScan Inc donated materials during the DPP
and DPPOS. The opinions expressed are those of the investigators and do
not necessarily reflect the views of the funding agencies. A complete
list of centers, investigators, and staff can be found in the
Supplemental Data.
NR 40
TC 8
Z9 8
U1 9
U2 10
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1754
EP 1761
DI 10.1210/jc.2015-3754
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400050
PM 26900641
ER
PT J
AU Yin, XY
Subramanian, S
Willinger, CM
Chen, G
Juhasz, P
Courchesne, P
Chen, BH
Li, XH
Hwang, SJ
Fox, CS
O'Donnell, CJ
Muntendam, P
Fuster, V
Bobeldijk-Pastorova, I
Sookoian, SC
Pirola, CJ
Gordon, N
Adourian, A
Larson, MG
Levy, D
AF Yin, Xiaoyan
Subramanian, Subha
Willinger, Christine M.
Chen, George
Juhasz, Peter
Courchesne, Paul
Chen, Brian H.
Li, Xiaohang
Hwang, Shih-Jen
Fox, Caroline S.
O'Donnell, Christopher J.
Muntendam, Pieter
Fuster, Valentin
Bobeldijk-Pastorova, Ivana
Sookoian, Silvia C.
Pirola, Carlos J.
Gordon, Neal
Adourian, Aram
Larson, Martin G.
Levy, Daniel
TI Metabolite Signatures of Metabolic Risk Factors and their Longitudinal
Changes
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CORONARY-HEART-DISEASE; LYSOPHOSPHATIDIC ACID; CARDIOVASCULAR-DISEASE;
ALANINE AMINOTRANSFERASE; INSULIN-RESISTANCE; LACTATE LEVELS; PLANT
STEROLS; STUDY DESIGN; AMINO-ACID; AUTOTAXIN
AB Context: Metabolic dysregulation underlies key metabolic risk factors-obesity, dyslipidemia, and dysglycemia.
Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor changes over time.
Design: Cross-sectional-discovery samples (n = 650; age, 36-69 years) from the Framingham Heart Study (FHS) and replication samples (n = 670; age, 61-76 years) from the BioImage Study, both following a factorial design sampled from high vs low strata of body mass index, lipids, and glucose. Longitudinal-FHS participants (n = 554) with 5-7 years of follow-up for risk factor changes.
Setting: Observational studies.
Participants: Cross-sectional samples with or without obesity, dysglycemia, and dyslipidemia, excluding prevalent cardiovascular disease and diabetes or dyslipidemia treatment. Age-and sex-matched by group.
Interventions: None.
Main Outcome Measure(s): Gas chromatography-mass spectrometry detected 119 plasma metabolites. Cross-sectional associations with obesity, dyslipidemia, and dysglycemia were tested in discovery, with external replication of 37 metabolites. Single-and multi-metabolite markers were tested for association with longitudinal changes in risk factors.
Results: Cross-sectional metabolite associations were identified with obesity (n = 26), dyslipidemia (n = 21), and dysglycemia (n = 11) in discovery. Glutamic acid, lactic acid, and sitosterol associated with all three risk factors in meta-analysis (P < 4.5 x 10(-4)). Metabolites associated with longitudinal risk factor changes were enriched for bioactive lipids. Multi-metabolite panels explained 2.5-15.3% of longitudinal changes in metabolic traits.
Conclusions: Cross-sectional results implicated dysregulated glutamate cycling and amino acid metabolism in metabolic risk. Certain bioactive lipids were associated with risk factors cross-sectionally and over time, suggesting their upstream role in risk factor progression. Functional studies are needed to validate findings and facilitate translation into treatments or preventive measures.
C1 [Yin, Xiaoyan; Subramanian, Subha; Willinger, Christine M.; Chen, George; Courchesne, Paul; Chen, Brian H.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.; Larson, Martin G.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
[Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02118 USA.
[Yin, Xiaoyan; Larson, Martin G.] Sch Publ Hlth, Boston, MA 02118 USA.
[Subramanian, Subha; Willinger, Christine M.; Chen, George; Chen, Brian H.; Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Juhasz, Peter; Li, Xiaohang; Muntendam, Pieter; Gordon, Neal; Adourian, Aram] BG Med Inc, 610 Lincoln St, Waltham, MA 02451 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Med Sch, Boston, MA 02115 USA.
[O'Donnell, Christopher J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Fuster, Valentin] Mt Sinai Sch Med, New York, NY 10029 USA.
[Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain.
[Bobeldijk-Pastorova, Ivana] TNO Triskel BV Inc, NL-3704 HE Zeist, Netherlands.
[Sookoian, Silvia C.; Pirola, Carlos J.] Univ Buenos Aires, Inst Med Res A Lanari IDIM, Natl Sci & Tech Res Council, C11428, Buenos Aires, DF, Argentina.
[Levy, Daniel] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Larson, MG; Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.; Adourian, A (reprint author), BG Med Inc, 610 Lincoln St, Waltham, MA 02451 USA.
EM aadourian@bg-medicine.com; mlarson@bu.edu; levyd@nih.gov
RI Fuster, Valentin/H-4319-2015
OI Fuster, Valentin/0000-0002-9043-9986
FU National Institutes of Health [N01-HC-25195]; Division of Intramural
Research of the National Heart, Lung, and Blood Institute
FX The Framingham Heart Study is funded by National Institutes of Health
contract N01-HC-25195; this research was also supported by the Division
of Intramural Research of the National Heart, Lung, and Blood Institute.
This study was made possible by a cooperative research and development
agreement between BG Medicine, Inc, Boston University, and the National
Heart, Lung, and Blood Institute.
NR 65
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U1 1
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1779
EP 1789
DI 10.1210/jc.2015-2555
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400053
PM 26908103
ER
PT J
AU Kassai, A
Muniyappa, R
Levenson, AE
Walter, MF
Abel, BS
Ring, M
Taylor, SI
Biddinger, SB
Skarulis, MC
Gorden, P
Brown, RJ
AF Kassai, Andrea
Muniyappa, Ranganath
Levenson, Amy E.
Walter, Mary F.
Abel, Brent S.
Ring, Michael
Taylor, Simeon I.
Biddinger, Sudha B.
Skarulis, Monica C.
Gorden, Phillip
Brown, Rebecca J.
TI Effect of Leptin Administration on Circulating Apolipoprotein CIII
levels in Patients With Lipodystrophy
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID C-III; NONFASTING TRIGLYCERIDES; LIPOPROTEIN METABOLISM; APOC-III; A-I;
RISK; RECEPTOR; INSULIN; LIPASE; MEN
AB Context: Apolipoprotein CIII (apoCIII), an inhibitor of lipoprotein lipase, plays an important role in triglyceride metabolism. However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown.
Objective: The objective of the study was to test the hypotheses that apoCIII is elevated in hypertriglyceridemic patients with lipodystrophy and that leptin replacement in these patients lowers circulating apoCIII.
Design, Setting, Study Participants, Intervention, and Outcome Measures: Using a post hoc crosssectional case-control design, we compared serum apoCIII levels from patients with lipodystrophy not associated with HIV (n = 60) and age-, gender-, race-, and ethnicity-matched controls (n = 54) participating in ongoing studies at the National Institutes of Health. In a prospective, open-label, ongoing study, we studied the effects of 6-12 months of leptin replacement on apoCIII in lipodystrophy patients as an exploratory outcome.
Results: ApoCIII was higher in lipodystrophy patients (geometric mean [25th and 75th percentiles]) (23.9 mg/dL [14.6, 40.3]) compared with controls (14.9 mg/dL [12.3, 17.7]) (P < .0001). ApoCIII and triglyceride levels were positively correlated in patients with lipodystrophy (R = 0.72, P < .0001) and healthy controls (R = 0.6, P < .0001). Leptin replacement (6-12 mo) did not significantly alter apoCIII (before leptin: 23.4 mg/dL [14.5, 40.1]; after leptin: 21.4 mg/dL [16.7, 28.3]; P = .34).
Conclusions: Leptin replacement in lipodystrophy did not alter serum apoCIII levels. Elevated apoCIII may play a role in the hypertriglyceridemia of lipodystrophy independent of leptin deficiency and replacement.
C1 [Kassai, Andrea; Muniyappa, Ranganath; Abel, Brent S.; Ring, Michael; Skarulis, Monica C.; Gorden, Phillip; Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Walter, Mary F.] NIDDK, Clin Core Lab, NIH, Bethesda, MD 20892 USA.
[Levenson, Amy E.; Biddinger, Sudha B.] Harvard Med Sch, Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Taylor, Simeon I.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
RP Brown, RJ (reprint author), NIDDK, NIH, Bldg 10-CRC,Room 6-5942,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brownrebecca@niddk.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases;
Inter-Institute Endocrinology Fellowship Program at the National
Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Institute of Diabetes and
Digestive and Kidney Diseases, and by the Inter-Institute Endocrinology
Fellowship Program at the National Institute of Diabetes and Digestive
and Kidney Diseases.
NR 31
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1790
EP 1797
DI 10.1210/jc.2015-3891
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400054
PM 26900642
ER
PT J
AU Larsen, BA
Wassel, CL
Kritchevsky, SB
Strotmeyer, ES
Criqui, MH
Kanaya, AM
Fried, LF
Schwartz, AV
Harris, TB
Ix, JH
AF Larsen, Britta A.
Wassel, Christina L.
Kritchevsky, Stephen B.
Strotmeyer, Elsa S.
Criqui, Michael H.
Kanaya, Alka M.
Fried, Linda F.
Schwartz, Ann V.
Harris, Tamara B.
Ix, Joachim H.
CA Hlth ABC Study
TI Association of Muscle Mass, Area, and Strength With Incident Diabetes in
Older Adults: The Health ABC Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SKELETAL-MUSCLE; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE;
BODY-COMPOSITION; ADIPOSE-TISSUE; WOMEN; RESISTANCE; MORTALITY; MEN;
OVERWEIGHT
AB Context: Skeletal muscle plays a key role in glucose regulation, yet the association between muscle quantity or quality and the risk of developing type 2 diabetes has not been explored.
Objective: The objective of the study was to assess the association between muscle quantity and strength and incident diabetes and to explore whether this association differs by body mass index (BMI) category.
Design and Setting: Participants were 2166 older adults in the Health, Aging, and Body Composition Study who were free of diabetes at baseline (1997-1998). Computed tomography and dual-energy x-ray absorptiometry were used to measure abdominal and thigh muscle area and total body lean mass, respectively. Strength was quantified by grip and knee extensions.
Main Outcome Measure: Incident diabetes, defined as fasting glucose of 126 mg/dL or greater, a physician's diagnosis, and/or the use of hypoglycemic medication were measured.
Results: After a median 11.3 years of follow-up, there were 265 incident diabetes cases (12.2%). In fully adjusted models, no association was found between muscle or strength measures and incident diabetes (for all, P > .05). For women, there was a significant interaction with BMI category for both abdominal and thigh muscle, such that greater muscle predicted lower risk of incident diabetes for normal-weight women(hazard ratio 0.37 [0.17-0.83] and 0.58 [0.27-1.27] per SD, respectively) and a greater risk for overweight and obese women(hazard ratio 1.23 [0.98-1.54] and 1.28 [1.00-1.64], respectively). No significant interactions by BMI category existed for strength measures or any measures for men (for all, P > .05).
Conclusions: Greater muscle area is associated with a lower risk of incident diabetes for older normal-weight women but not for men or overweight women.
C1 [Larsen, Britta A.; Criqui, Michael H.; Ix, Joachim H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, San Diego, CA 92093 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA.
[Wassel, Christina L.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT 05446 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27157 USA.
[Kritchevsky, Stephen B.] Sch Med, Winston Salem, NC 27157 USA.
[Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15219 USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Div Gen Internal Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA.
[Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RP Larsen, BA (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, San Diego, CA 92093 USA.
EM blarsen@ucsd.edu
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
Grant [R01-NR012459]; Intramural Research Program of the National
Institute on Aging; Career Development Grant from National Institute of
Diabetes and Digestive and Kidney Diseases [K01 DK101650]; Established
Investigator Award from American Heart Association [14EIA18560026]
FX This work was supported Contracts N01-AG-6-2101, N01-AG-6-2103, and
N01-AG-6-2106 from the National Institute on Aging, National Institute
on Aging Grant R01-AG028050 and National Institute of Nursing Research
Grant R01-NR012459. This research was also supported in part by the
Intramural Research Program of the National Institute on Aging. B.L. was
supported by Career Development Grant K01 DK101650 from the National
Institute of Diabetes and Digestive and Kidney Diseases. J.I. was
supported by an Established Investigator Award from the American Heart
Association (14EIA18560026).
NR 26
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1847
EP 1855
DI 10.1210/jc.2015-3643
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400060
PM 26930180
ER
PT J
AU Wang, XY
Jung, M
Mossavar-Rahmani, Y
Sotres-Alvarez, D
Giacinto, RAE
Pirzada, A
Reina, SA
Casagrande, SS
Wang, T
Aviles-Santa, ML
Kaplan, RC
Qi, QB
AF Wang, Xueyin
Jung, Molly
Mossavar-Rahmani, Yasmin
Sotres-Alvarez, Daniela
Giacinto, Rebeca A. Espinoza
Pirzada, Amber
Reina, Samantha A.
Casagrande, Sarah S.
Wang, Tao
Aviles-Santa, M. Larissa
Kaplan, Robert C.
Qi, Qibin
TI Macronutrient Intake, Diagnosis Status, and Glycemic Control Among US
Hispanics/Latinos With Diabetes
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; MONOUNSATURATED FATTY-ACIDS;
ETHNIC-DIFFERENCES; LATINO POPULATION; NATIONAL-HEALTH; ENERGY-INTAKE;
WEIGHT-LOSS; ADULTS; DIET; THERAPY
AB Context: Diet modification is a mainstay of diabetes management. US Hispanics/Latinos are disproportionately affected by diabetes, but few studies have examined dietary intake among US Hispanics/Latinos with diabetes, and little is known regarding the influence of diabetes awareness on dietary intake.
Objective: We evaluated macronutrient intake and its associations with diabetes awareness and glycemic control among US Hispanics/Latinos with diabetes.
Participants: This analysis included 3310 diabetic adults aged 18-74 years from the Hispanic Community Health Study/Study of Latinos (2008-2011).
Main Outcome Measures: Diabetes was defined as diagnosed (based on medical history or antihyperglycemic medication use) or undiagnosed diabetes (based on fasting glucose >= 126 mg/dL, glycated hemoglobin [ HbA1c] >= 6.5%, or 2 h glucose >= 200 mg/dL in the absence of a physician diagnosis). Dietary intake was assessed using two 24-hour recalls.
Results: Among Hispanic/Latino adults with diabetes, 21.2%, 55.7%, and 71.2% met the American Diabetes Association recommendations for fiber (>= 14 g per 1000 kcal), saturated fat (< 10% of total energy), and cholesterol intake (< 300 mg), respectively. Compared with those with undiagnosed diabetes, people with diagnosed diabetes consumed less carbohydrate (50.3 vs 52.4% of total energy; P = .017), total sugar (19.1 vs 21.5% of total energy; P = .002), added sugar (9.8 vs 12.1% of total energy; P < .001), and more total fat (30.7 vs 29.3% of total energy; P = .048) and monounsaturated fat (11.5 vs 10.7% of total energy; P = .021). Association between diabetes awareness and low total and added sugar intake was observed in individuals of Mexican and Puerto Rican background but not in other groups (P for interaction < .05). Among people with diagnosed diabetes, those with HbA1c of 7% or greater consumed more total fat, saturated fat, and cholesterol than those with HbA1c less than 7% (all P < .05).
Conclusions: Among US Hispanics/Latinos with diabetes, fiber intake is low, and diabetes awareness is associated with reduced carbohydrate and sugar intake and increased monounsaturated fat intake. Sugar intake may require special attention in certain Hispanic/Latino background groups.
C1 [Wang, Xueyin; Jung, Molly; Mossavar-Rahmani, Yasmin; Wang, Tao; Kaplan, Robert C.; Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
[Wang, Xueyin] Peking Univ, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China.
[Sotres-Alvarez, Daniela] Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Giacinto, Rebeca A. Espinoza] San Diego State Univ, San Diego, CA 92182 USA.
[Pirzada, Amber] Univ Illinois, Inst Minor Hlth Res, Chicago, IL 60637 USA.
[Reina, Samantha A.] Univ Miami, Dept Psychol, Miami, FL 33136 USA.
[Casagrande, Sarah S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Aviles-Santa, M. Larissa] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20824 USA.
RP Qi, QB (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM qibin.qi@einstein.yu.edu
RI DeMarcus, Forrest/O-9190-2016; Sotres-Alvarez, Daniela/O-9085-2016
OI Sotres-Alvarez, Daniela/0000-0002-3226-6140
FU National Heart, Lung, and Blood Institute [N01-HC65233]; University of
Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235];
Northwestern University [N01-HC65236]; San Diego State University
[N01-HC65237]; China Scholarship Council
FX This work was supported by contracts from the National Heart, Lung, and
Blood Institute to the University of North Carolina (N01-HC65233),
University of Miami (N01-HC65234), Albert Einstein College of Medicine
(N01-HC65235), Northwestern University (N01-HC65236), and San Diego
State University (N01-HC65237). The following institutes/centers/offices
contributed to the Hispanic Community Health Study/Study of Latinos
through a transfer of funds to the National Heart, Lung, and Blood
Institute: National Center on Minority Health and Health Disparities,
the National Institute of Deadness and Other Communications Disorders,
the National Institute of Dental and Craniofacial Research, the National
Institute of Diabetes and Digestive and Kidney Diseases, the National
Institute of Neurological Disorders and Stroke, and the Office of
Dietary Supplements. X.W. was supported by the China Scholarship
Council.
NR 32
TC 1
Z9 1
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1856
EP 1864
DI 10.1210/jc.2015-3237
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400061
PM 26950682
ER
PT J
AU Dias, JP
Melvin, D
Shardell, M
Ferrucci, L
Chia, CW
Gharib, M
Egan, JM
Basaria, S
AF Dias, Jenny Pena
Melvin, Denise
Shardell, Michelle
Ferrucci, Luigi
Chia, Chee W.
Gharib, Mohsen
Egan, Josephine M.
Basaria, Shehzad
TI Effects of Transdermal Testosterone Gel or an Aromatase Inhibitor on
Prostate Volume in Older Men
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ESTROGEN-RECEPTOR-BETA; MIDDLE-AGED MEN; HYPOGONADAL MEN; REPLACEMENT
THERAPY; ANDROGEN RECEPTOR; CONTROLLED-TRIAL; DOG PROSTATE; ELDERLY-MEN;
HYPERPLASIA; CANCER
AB Context: T replacement is being increasingly offered to older men with age-related low T; hence, monitoring prostate health is important during T therapy. Data suggest that estrogens have an independent effect on the prostate and some effects of T on the prostate might be mediated via its aromatization to estradiol. Although some studies have assessed the effects of T replacement on prostate volume, the differential effects of T and estradiol have not been delineated.
Objective: The objective of the study was to investigate the relative effects of T and estradiol on prostate volume in older men with low T.
Participants: Thirty-one men, 65 years old or older with total T less than 350 ng/dL (measured by mass spectrometry) participated in the study.
Intervention: The intervention included randomization to 5 g transdermal T gel (TT), 1 mg oral aromatase inhibitor (AI), or placebo daily for 12 months.
Main Outcome Measures: The primary outcome was prostate volume measured by transrectal ultrasound at baseline and 12 months. Secondary outcomes included prostate-specific antigen levels and lower urinary tract symptoms score.
Results: Serum T levels increased in both intervention groups; estradiol levels increased in the TT group, whereas it decreased in the AI group. At 12 months, prostate volume significantly increased (4.5 +/- 1.76 cc, P < .05) only in the TT group. Increase in prostate-specific antigen levels were seen in both intervention groups at 6 months (P < .01 and P < .001). The lower urinary tract symptoms score increased only in the TT group (P < .05).
Conclusion: The tropic effects of T on the prostate are mediated via its aromatization to estradiol. Administration of AI for 12 months to older men was not detrimental to the prostate.
C1 [Dias, Jenny Pena; Melvin, Denise; Egan, Josephine M.] Medstar Harbor Hosp, Lab Clin Invest, Baltimore, MD 21225 USA.
[Shardell, Michelle; Ferrucci, Luigi; Chia, Chee W.] Medstar Harbor Hosp, Translat Gerontol Branch, Baltimore, MD 21225 USA.
[Gharib, Mohsen] Medstar Harbor Hosp, NIA, Baltimore, MD 21225 USA.
[Gharib, Mohsen] Medstar Harbor Hosp, Imaging Sect, Baltimore, MD 21225 USA.
[Basaria, Shehzad] Harvard Med Sch, Sect Mens Hlth Aging & Metab, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Basaria, S (reprint author), Harvard Med Sch, Sect Mens Hlth Aging & Metab, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM sbasaria@partners.org
FU Intramural Research Program of National Institute on Aging, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 48
TC 0
Z9 0
U1 3
U2 3
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD APR
PY 2016
VL 101
IS 4
BP 1865
EP 1871
DI 10.1210/jc.2016-1111
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU0YP
UT WOS:000381931400062
PM 26950683
ER
PT J
AU Baron, KB
Choi, AD
Chen, MY
AF Baron, Kaitlin B.
Choi, Andrew D.
Chen, Marcus Y.
TI Low Radiation Dose Calcium Scoring: Evidence and Techniques
SO CURRENT CARDIOVASCULAR IMAGING REPORTS
LA English
DT Article
DE Coronary artery calcium (CAC) scoring; Low dose radiation; Iterative
Reconstruction; Rescan variability; Coronary artery disease; Computed
tomography (CT); Atherosclerotic cardiovascular disease (ASCVD)
ID CORONARY-ARTERY CALCIUM; STATISTICAL ITERATIVE RECONSTRUCTION; FILTERED
BACK-PROJECTION; COMPUTED-TOMOGRAPHY; IMAGE-RECONSTRUCTION;
AMERICAN-COLLEGE; CT; IMPACT; QUANTIFICATION; REDUCTION
AB Coronary computed tomography (CT) allows for the acquisition of thin slices of the heart and coronary arteries, which can be used to detect and quantify coronary artery calcium (CAC), a marker of atherosclerotic cardiovascular disease. Despite the proven clinical value in cardiac risk prognostication, there remain concerns regarding radiation exposure from CAC CT scans. There have been several recent technical advancements that allow for significant radiation dose reduction in CAC scoring. This paper reviews the clinical utility and recent literature in low radiation dose CAC scoring.
C1 [Baron, Kaitlin B.; Choi, Andrew D.] George Washington Univ, Div Cardiol, Sch Med, Washington, DC USA.
[Choi, Andrew D.; Chen, Marcus Y.] NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH, 10 Ctr Dr,Bldg 10,B1D416, Bethesda, MD 20891 USA.
RP Chen, MY (reprint author), NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH, 10 Ctr Dr,Bldg 10,B1D416, Bethesda, MD 20891 USA.
EM Marcus.Chen@nih.gov
NR 41
TC 3
Z9 3
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1941-9066
EI 1941-9074
J9 CURR CARDIOVASC IMAG
JI CURR. CARDIOVASC. IMAGING REP.
PD APR
PY 2016
VL 9
IS 4
AR UNSP 12
DI 10.1007/s12410-016-9373-1
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DU5KD
UT WOS:000382249700001
ER
PT J
AU Han, JF
An, SJ
Su, WM
Chen, ZH
Su, J
Yan, HH
Guo, WB
Chen, SL
Huang, Y
Xie, Z
Lan, Q
Rothman, N
Wu, YL
Yang, JJ
AF Han, Jie-Fei
An, She-Juan
Su, Wen-Mei
Chen, Zhi-Hong
Su, Jian
Yan, Hong-hong
Guo, Wei-Bang
Chen, Shi-Liang
Huang, Ying
Xie, Zhi
Lan, Qing
Rothman, Nathaniel
Wu, Yi-Long
Yang, Jin-Ji
TI Polymorphism of rs9387478 correlates with overall survival in female
nonsmoking patients with lung cancer
SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS
LA English
DT Article
DE EGFR mutation; Lung cancer; Overall survival; Polymorphism
ID GENOME-WIDE ASSOCIATION; NEVER SMOKERS; ROS1 REARRANGEMENT; RISK;
ADENOCARCINOMA; SUSCEPTIBILITY; EXPRESSION; PROLIFERATION; CHEMOTHERAPY;
POPULATION
AB Background: Our previous study identified rs9387478 as a new susceptibility locus associated with lung cancer in never-smoking women in Asia; however, the clinical and prognostic significance of this finding is not known.
Methods: We analyzed the relationship between the rs9387478 single nucleotide polymorphism and i) clinical parameters and ii) overall survival time in 505 female nonsmoking lung cancer patients, using the chi-square test and Kaplan-Meier analysis with the log-rank test, respectively. We further established the epidermal growth factor receptor (EGFR) mutation status and assessed its association with rs9387478 genotypes as well as the efficacy of EGFR tyrosine kinase inhibitors.
Results: The frequency of the AA genotype was significantly higher in the EGFR-mutation-negative group than in the EGFR-mutation-positive group (32% vs. 16%, chi(2) = 13.025, p = 0.011). Patients with the CC genotype had a better overall survival time than patients with the AA/AC genotype (median survival time: 54.2 vs. 32.9 months,chi(2) = 4.593, p = 0.032). The distribution of rs9387478 genotypes differed according to the clinical disease stage.
Conclusions: This study indicates that the rs9387478 genotype was associated with overall survival in nonsmoking female patients with lung cancer, although it was not significant after adjusting for multiple testing. The identification of the location of the rs9387478 single nucleotide polymorphism in the genomic interval containing the DCBLD1 and ROS1 genes, together with the finding that the rs9387478 polymorphism correlates with EGFR mutation status, may have important implications for therapeutic approaches targeting EGFR or ROS1 in patients with lung cancer.
C1 [Han, Jie-Fei] Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
[Han, Jie-Fei; An, She-Juan; Su, Wen-Mei; Chen, Zhi-Hong; Su, Jian; Yan, Hong-hong; Guo, Wei-Bang; Chen, Shi-Liang; Huang, Ying; Xie, Zhi; Wu, Yi-Long; Yang, Jin-Ji] Guangdong Gen Hosp, Guangdong Lung Canc Inst, 106 Zhongshan 2 Rd, Guangzhou 510080, Guangdong, Peoples R China.
[Han, Jie-Fei; An, She-Juan; Su, Wen-Mei; Chen, Zhi-Hong; Su, Jian; Yan, Hong-hong; Guo, Wei-Bang; Chen, Shi-Liang; Huang, Ying; Xie, Zhi; Wu, Yi-Long; Yang, Jin-Ji] Guangdong Acad Med Sci, Guangdong Key Lab Lung Canc Translat Med, Guangzhou, Guangdong, Peoples R China.
[Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Yang, JJ (reprint author), Guangdong Gen Hosp, Guangdong Lung Canc Inst, 106 Zhongshan 2 Rd, Guangzhou 510080, Guangdong, Peoples R China.; Yang, JJ (reprint author), Guangdong Acad Med Sci, Guangdong Key Lab Lung Canc Translat Med, Guangzhou, Guangdong, Peoples R China.
EM yangjinji2003@163.com
FU National Natural Science Foundation of China [81101549, 30772531,
81272618]; Nonprofit Research and Special Projects of National Health
and Family Planning Committee of China [201402031]
FX This work was supported by the National Natural Science Foundation of
China (Nos. 81101549, 30772531 and 81272618) and Nonprofit Research and
Special Projects of National Health and Family Planning Committee of
China (No. 201402031).
NR 35
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Z9 0
U1 1
U2 1
PU WICHTIG PUBLISHING
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 0393-6155
EI 1724-6008
J9 INT J BIOL MARKER
JI Int. J. Biol. Markers
PD APR-JUN
PY 2016
VL 31
IS 2
BP E144
EP E152
DI 10.5301/jbm.5000180
PG 9
WC Biotechnology & Applied Microbiology; Oncology
SC Biotechnology & Applied Microbiology; Oncology
GA DS7KT
UT WOS:000380963100006
PM 26689248
ER
PT J
AU Nair, RP
Zheng, CY
Sunavala-Dossabhoy, G
AF Nair, Renjith Parameswaran
Zheng, Changyu
Sunavala-Dossabhoy, Gulshan
TI Retroductal Submandibular Gland Instillation and Localized Fractionated
Irradiation in a Rat Model of Salivary Hypofunction
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 110; Human Gene Therapy; Volume 24; salivary gland;
cannulation; collimation; fractions; ionizing radiation; rat; animal
model; salivary hypofunction
ID RADIATION-INDUCED XEROSTOMIA; GENE THERAPEUTICS; PROTECTION; DELIVERY;
DAMAGE; CDNA
AB Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. Irreparable cell damage results in a chronic loss of salivary function that impairs basic oral activities, and increases the risk of oral infections and dental caries. Salivary hypofunction and its complications gravely impact a patient's comfort. Current symptomatic management of the condition is ineffective, and newer therapies to assuage the condition are needed.
Salivary glands are exocrine glands, which expel their secretions into the mouth via excretory ducts. Cannulation of these ducts provides direct access to the glands. Retroductal delivery of a contrast agent to major salivary glands is a routine out-patient procedure for diagnostic imaging. Using a similar procedure, localized treatment of the glands is feasible. However, performing this technique in preclinical studies with small animals poses unique challenges. In this study we describe the technique of retroductal administration in rat submandibular glands, a procedure that was refined in Dr. Bruce Baum's laboratory (NIH)(1), and lay out a procedure for local gland irradiation.
C1 [Nair, Renjith Parameswaran; Sunavala-Dossabhoy, Gulshan] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Baton Rouge, LA 70803 USA.
[Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD USA.
RP Sunavala-Dossabhoy, G (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Baton Rouge, LA 70803 USA.
EM GSunav@lsuhsc.edu
FU American Cancer Society [116945-RSG-09-038-01-CCE]; National Institute
of Health [R21CA173162]; Feist-Weiller Cancer Center
FX We thank Dr. John Chang (Radiation Oncology, LSU Health Science Center)
for assistance with radiation dose measurements. The study was supported
by the American Cancer Society (Grant number: 116945-RSG-09-038-01-CCE),
National Institute of Health (Grant number: R21CA173162) and the
Feist-Weiller Cancer Center.
NR 21
TC 0
Z9 0
U1 1
U2 1
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD APR
PY 2016
IS 110
AR e53785
DI 10.3791/53785
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR9ZX
UT WOS:000380256000040
ER
PT J
AU Blackley, DJ
Wiley, MR
Ladner, JT
Fallah, M
Lo, T
Gilbert, ML
Gregory, C
D'ambrozio, J
Coulter, S
Mate, S
Balogun, Z
Kugelman, J
Nwachukwu, W
Prieto, K
Yeiah, A
Amegashie, F
Kearney, B
Wisniewski, M
Saindon, J
Schroth, G
Fakoli, L
Diclaro, JW
Kuhn, JH
Hensley, LE
Jahrling, PB
Stroher, U
Nichol, ST
Massaquoi, M
Kateh, F
Clement, P
Gasasira, A
Bolay, F
Monroe, SS
Rambaut, A
Sanchez-Lockhart, M
Laney, AS
Nyenswah, T
Christie, A
Palacios, G
AF Blackley, David J.
Wiley, Michael R.
Ladner, Jason T.
Fallah, Mosoka
Lo, Terrence
Gilbert, Merle L.
Gregory, Christopher
D'ambrozio, Jonathan
Coulter, Stewart
Mate, Suzanne
Balogun, Zephaniah
Kugelman, Jeffrey
Nwachukwu, William
Prieto, Karla
Yeiah, Adolphus
Amegashie, Fred
Kearney, Brian
Wisniewski, Meagan
Saindon, John
Schroth, Gary
Fakoli, Lawrence
Diclaro, Joseph W., II
Kuhn, Jens H.
Hensley, Lisa E.
Jahrling, Peter B.
Stroher, Ute
Nichol, Stuart T.
Massaquoi, Moses
Kateh, Francis
Clement, Peter
Gasasira, Alex
Bolay, Fatorma
Monroe, Stephan S.
Rambaut, Andrew
Sanchez-Lockhart, Mariano
Laney, A. Scott
Nyenswah, Tolbert
Christie, Athalia
Palacios, Gustavo
TI Reduced evolutionary rate in reemerged Ebola virus transmission chains
SO SCIENCE ADVANCES
LA English
DT Article
ID LIBERIA; SURVEILLANCE; OUTBREAK; SPREAD
AB On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.
C1 [Blackley, David J.; Lo, Terrence; Gregory, Christopher; Coulter, Stewart; Balogun, Zephaniah; Nwachukwu, William; Saindon, John; Stroher, Ute; Monroe, Stephan S.; Laney, A. Scott; Christie, Athalia] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
[Wiley, Michael R.; Ladner, Jason T.; Gilbert, Merle L.; D'ambrozio, Jonathan; Mate, Suzanne; Kugelman, Jeffrey; Prieto, Karla; Kearney, Brian; Wisniewski, Meagan; Sanchez-Lockhart, Mariano; Palacios, Gustavo] US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Fallah, Mosoka; Yeiah, Adolphus; Amegashie, Fred; Massaquoi, Moses; Kateh, Francis; Nyenswah, Tolbert] Minist Hlth, Monrovia, Liberia.
[Schroth, Gary] Illumina Inc, San Diego, CA 92122 USA.
[Fakoli, Lawrence; Bolay, Fatorma] Liberian Inst Biomed Res, Charlesville, Liberia.
[Diclaro, Joseph W., II] US Navy, Naval Med Res Unit 3, Cairo, Egypt.
[Kuhn, Jens H.; Hensley, Lisa E.; Jahrling, Peter B.; Nichol, Stuart T.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Clement, Peter; Gasasira, Alex] WHO, CH-1211 Geneva 27, Switzerland.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3FL, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland.
RP Christie, A (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.; Palacios, G (reprint author), US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA.; Nyenswah, T (reprint author), Minist Hlth, Monrovia, Liberia.
EM tgnyenswah74@yahoo.com; akc9@cdc.gov; gustavo.f.palacios.ctr@mail.mil
RI Palacios, Gustavo/I-7773-2015
OI Palacios, Gustavo/0000-0001-5062-1938
FU NIAID NIH HHS [HHSN272200700016I]; PHS HHS [HHSN272200700016I]
NR 25
TC 7
Z9 7
U1 1
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 2375-2548
J9 SCI ADV
JI Sci. Adv.
PD APR
PY 2016
VL 2
IS 4
AR e1600378
DI 10.1126/sciadv.1600378
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR7IB
UT WOS:000380072100053
PM 27386513
ER
PT J
AU Shah, NG
Seam, N
Woods, CJ
Fessler, HE
Goyal, M
McAreavey, D
Lee, BW
AF Shah, Nirav G.
Seam, Nitin
Woods, Christian J.
Fessler, Henry E.
Goyal, Munish
McAreavey, Dorothea
Lee, Burton W.
CA DC Baltimore Critical Care Educati
TI A Longitudinal Regional Educational Model for Pulmonary and Critical
Care Fellows Emphasizing Small Group- and Simulation-based Learning
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Recent trends have necessitated a renewed focus on how we deliver formal didactic and simulation experiences to pulmonary and critical care medicine (PCCM) fellows. To address the changing demands of training PCCM fellows, as well as the variability in the clinical training, fund of knowledge, and procedural competence of incoming fellows, we designed a PCCM curriculum that is delivered regionally in the Baltimore/Washington, DC area in the summer and winter. The educational curriculum began in 2008 as a collaboration between the Critical Care Medicine Department at the National Institutes of Health and the Pulmonary and Critical Care Section of the Department of Medicine at MedStar Washington Hospital Center and now includes 13 individual training programs in PCCM, critical care medicine, and pulmonary diseases in Baltimore and Washington, DC. Informal and formal feedback from the fellows who participated led to substantial changes to the course curriculum, allowing for continuous improvement. The educational consortium has helped build a local community of educators to share ideas, support each other's career development, and collaborate on other endeavors. In this article, we describe how we developed and deliver this curriculum and report on lessons learned.
C1 [Shah, Nirav G.] Univ Maryland, Sch Med, Div Pulm & Crit Care, Baltimore, MD USA.
[Seam, Nitin; McAreavey, Dorothea; Lee, Burton W.] NIH, Dept Crit Care Med, Bethesda, MD USA.
[Woods, Christian J.; Goyal, Munish; Lee, Burton W.] MedStar Washington Hosp Ctr, Div Pulm Crit Care & Resp Serv, Washington, DC USA.
[Goyal, Munish] MedStar Washington Hosp Ctr, Dept Emergency Med, Washington, DC USA.
[Fessler, Henry E.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care, Baltimore, MD USA.
[Lee, Burton W.] AIC Kijabe Hosp, Dept Med, Kijabe, Kenya.
RP Shah, NG (reprint author), Univ Maryland, Med Ctr, 110 S Paca St,2nd Floor,Room 2-N-144, Baltimore, MD 21201 USA.
EM nshah1@medicine.umaryland.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD APR
PY 2016
VL 13
IS 4
BP 469
EP 474
DI 10.1513/AnnalsATS.201601-027AR
PG 6
WC Respiratory System
SC Respiratory System
GA DR6BT
UT WOS:000379986900007
PM 26845063
ER
PT J
AU Duncan, GA
Lockett, A
Villegas, LR
Almodovar, S
Gomez, JL
Flores, SC
Wilkes, DS
Tigno, XT
AF Duncan, Gregg A.
Lockett, Angelia
Villegas, Leah R.
Almodovar, Sharilyn
Gomez, Jose L.
Flores, Sonia C.
Wilkes, David S.
Tigno, Xenia T.
TI National Heart, Lung, and Blood Institute Workshop Summary: Enhancing
Opportunities for Training and Retention of a Diverse Biomedical
Workforce
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Rationale: Committed to its mission of conducting and supporting research that addresses the health needs of all sectors of the nation's population, the Division of Lung Diseases, National Heart, Lung, and Blood Institute of the National Institutes of Health (NHLBI/NIH) seeks to identify issues that impact the training and retention of underrepresented individuals in the biomedical research workforce.
Objectives: Early-stage investigators who received grant support through the NIH Research Supplements to Promote Diversity in Health Related Research Program were invited to a workshop held in Bethesda, Maryland in June, 2015, in order to (1) assess the effectiveness of the current NHLBI diversity program, (2) improve its strategies towards achieving its goal, and (3) provide guidance to assist the transition of diversity supplement recipients to independent NIH grant support.
Methods: Workshop participants participated in five independent focus groups to discuss specific topics affecting underrepresented individuals in the biomedical sciences: (1) Socioeconomic barriers to success for diverse research scientists; (2) role of the academic research community in promoting diversity; (3) life beyond a research project grant: non-primary investigator career paths in research; (4) facilitating career development of diverse independent research scientists through NHLBI diversity programs; and (5) effectiveness of current NHLBI programs for promoting diversity of the biomedical workforce.
Measurements and Main Results: Several key issues experienced by young, underrepresented biomedical scientists were identified, and solutions were proposed to improve on training and career development for diverse students, from the high school to postdoctoral trainee level, and address limitations of currently available diversity programs. Although some of the challenges mentioned, such as cost of living, limited parental leave, and insecure extramural funding, are also likely faced by nonminority scientists, these issues are magnified among diversity scientists and are complicated by unique circumstances in this group, such as limited exposure to science at a young age, absence of role models and mentors from underrepresented backgrounds, and social norms that relegate their career endeavors, particularly among women, to being subordinate to their expected cultural role.
Conclusions: The factors influencing the participation of underrepresented minorities in the biomedical workforce are complex and span several continuous or overlapping stages in the professional development of scientists from these groups. Therefore, amultipronged approach is needed to enable the professional development and retention of underrepresented minorities in biomedical research. This approach should address both individual and social factors and should involve funding agencies, academic institutions, mentoring teams, professional societies, and peer collaboration. Implementation of some of the recommendations, such as access to child care, institutional support and health benefits for trainees, teaching and entrepreneurial opportunities, grant-writing webinars, and pre-NIH career development (Pre-K) pilot programs would not only benefit biomedical scientists from underrepresented groups but also improve the situation of nondiverse junior scientists. However, other issues, such as opportunities for early exposure to science of disadvantaged/minority groups, and identifying mentors/life coaches/peer mentors who come from similar cultural backgrounds and vantage points, are unique to this group.
C1 [Duncan, Gregg A.] Johns Hopkins Univ, Sch Med, Ctr Nanomed, Baltimore, MD USA.
[Lockett, Angelia] Indiana Univ Sch Med, Dept Physiol, Indianapolis, IN USA.
[Wilkes, David S.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
[Wilkes, David S.] Indiana Univ Sch Med, Dept Microbiol, Indianapolis, IN USA.
[Wilkes, David S.] Indiana Univ Sch Med, Dept Immunol, Indianapolis, IN USA.
[Villegas, Leah R.] Univ Colorado Anschutz Med Campus, Dept Pediat & Cardiovasc Pulm Res, Aurora, CO USA.
[Almodovar, Sharilyn; Flores, Sonia C.] Univ Colorado Anschutz Med Campus, Div Pulm Sci & Crit Care Med, Aurora, CO USA.
[Gomez, Jose L.] Yale Univ, Sch Med, Dept Pulm Crit Care & Sleep Med, New Haven, CT USA.
[Tigno, Xenia T.] NHLBI, Div Lung Dis, NIH, Bethesda, MD USA.
RP Wilkes, DS (reprint author), Univ Virginia, Sch Med, POB 800793, Charlottesville, VA 22908 USA.
EM dsw4n@hscmail.mcc.virginia.edu
NR 0
TC 0
Z9 0
U1 2
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD APR
PY 2016
VL 13
IS 4
BP 562
EP 567
DI 10.1513/AnnalsATS.201509-624OT
PG 6
WC Respiratory System
SC Respiratory System
GA DR6BT
UT WOS:000379986900020
PM 27058184
ER
PT J
AU Nikitskaya, EA
Grive, JC
Maryukhnich, EV
Lebedeva, AM
Ivanova, OI
Savvinova, PP
Shpektor, AV
Margolis, LB
Vasilieva, EY
AF Nikitskaya, E. A.
Grive, J. -C.
Maryukhnich, E. V.
Lebedeva, A. M.
Ivanova, O. I.
Savvinova, P. P.
Shpektor, A. V.
Margolis, L. B.
Vasilieva, E. Yu.
TI Cytomegalovirus in Plasma of Acute Coronary Syndrome Patients
SO ACTA NATURAE
LA English
DT Article
DE coronary artery disease; acute coronary syndrome; human herpes viruses;
cytomegalovirus; polymerase chain reaction
ID HERPES-SIMPLEX-VIRUS; MYOCARDIAL-INFARCTION; CHLAMYDIA-PNEUMONIAE; ESC
GUIDELINES; ATHEROSCLEROSIS; INFECTION; RISK; DISEASE; ANGIOGRAPHY;
MECHANISMS
AB The relationship between acute coronary syndrome (ACS) and local and systemic inflammation, including accumulation of macrophages in atherosclerotic plaques and upregulation of blood cytokines (e.g., C-reactive protein (CRP)), has been known for more than 100 years. The atherosclerosis-associated inflammatory response has been traditionally considered as an immune system reaction to low-density lipoproteins. At the same time, some data have indicated a potential involvement of cytomegalovirus (CMV) in the activation and progression of atherosclerosis-associated inflammation, leading to ACS. However, these data have been tangential and mainly concerned the relationship between a coronary artery disease (CAD) prognosis and the anti-CMV antibody titer. We assumed that ACS might be associated with CMV reactivation and virus release into the bloodstream. The study's aim was to test this assumption through a comparison of the plasma CMV DNA level in patients with various CAD forms and in healthy subjects. To our knowledge, no similar research has been undertaken yet. A total of 150 subjects (97 CAD patients and 53 healthy subjects) were examined. Real-time polymerase chain reaction (RT-PCR) was used to determine the number of plasma CMV DNA copies. We demonstrated that the number of plasma CMV genome copies in ACS patients was significantly higher than that in healthy subjects (p = 0.01). The CMV genome copy number was correlated with the plasma CRP level (p = 0.002). These findings indicate a potential relationship between CMV activation and atherosclerosis exacerbation that, in turn, leads to the development of unstable angina and acute myocardial infarction. Monitoring of the CMV plasma level in CAD patients may be helpful in the development of new therapeutic approaches to coronary atherosclerosis treatment.
C1 [Nikitskaya, E. A.; Maryukhnich, E. V.; Lebedeva, A. M.; Ivanova, O. I.; Savvinova, P. P.; Shpektor, A. V.; Vasilieva, E. Yu.] Evdokimov Moscow State Univ Med & Dent, Dept Cardiol, Lab Afherothrombosis, Delegatskaya Str 20-1, Moscow 127473, Russia.
[Grive, J. -C.; Margolis, L. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD USA.
[Grive, J. -C.] Sidra Med & Res Ctr, POB 26999, Doha, Qatar.
RP Vasilieva, EY (reprint author), Evdokimov Moscow State Univ Med & Dent, Dept Cardiol, Lab Afherothrombosis, Delegatskaya Str 20-1, Moscow 127473, Russia.
EM vasilievahelena@gmail.com
RI Ivanova, Oxana/L-8578-2016
OI Ivanova, Oxana/0000-0002-8477-9706
FU Ministry of Education and Science of the Russian Federation
[14.V25.31.0016]
FX This work was supported by a grant of the Ministry of Education and
Science of the Russian Federation (o. 14.V25.31.0016).
NR 44
TC 1
Z9 1
U1 0
U2 0
PU RUSSIAN FEDERATION AGENCY SCIENCE & INNOVATION
PI MOSCOW
PA NAUCHNY PARK MGU, VLAD 1, STROENIYE 75G, LENINSKIYE GORY, MOSCOW,
119991, RUSSIA
SN 2075-8251
J9 ACTA NATURAE
JI Acta Naturae
PD APR-JUN
PY 2016
VL 8
IS 2
BP 102
EP 107
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DR0WV
UT WOS:000379628500012
PM 27437144
ER
PT J
AU Jonsdottir, G
Lund, SH
Bjorkholm, M
Turesson, I
Wahlin, A
Mailankody, S
Blimark, C
Hultcrantz, M
Porwit, A
Landgren, O
Kristinsson, SY
AF Jonsdottir, Gudbjorg
Lund, Sigrun H.
Bjorkholm, Magnus
Turesson, Ingemar
Wahlin, Anders
Mailankody, Sham
Blimark, Cecilie
Hultcrantz, Malin
Porwit, Anna
Landgren, Ola
Kristinsson, Sigurdur Y.
TI Survival in multiple myeloma patients who develop second malignancies: a
population-based cohort study
SO HAEMATOLOGICA
LA English
DT Letter
DE multiple myeloma; second malignancy; survival; population-based
ID LEUKEMIA; THERAPY
C1 [Jonsdottir, Gudbjorg; Lund, Sigrun H.; Kristinsson, Sigurdur Y.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Bjorkholm, Magnus; Hultcrantz, Malin; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.
[Bjorkholm, Magnus; Hultcrantz, Malin; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden.
[Turesson, Ingemar] Skane Univ Hosp, Dept Hematol & Coagulat Disorders, Malmo, Sweden.
[Wahlin, Anders] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden.
[Mailankody, Sham] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
[Blimark, Cecilie] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, Gothenburg, Sweden.
[Porwit, Anna] Univ Hlth Network, Dept Lab Med & Pathobiol, Toronto Gen Hosp, Toronto, ON, Canada.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA.
RP Kristinsson, SY (reprint author), Univ Iceland, Fac Med, Reykjavik, Iceland.; Kristinsson, SY (reprint author), Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.; Kristinsson, SY (reprint author), Karolinska Inst, Stockholm, Sweden.
EM sigurdur.Kristinsson@ki.se
RI Lund, Sigrun Helga/K-9144-2015
OI Lund, Sigrun Helga/0000-0002-3806-2296
NR 15
TC 3
Z9 3
U1 1
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD APR
PY 2016
VL 101
IS 4
DI 10.3324/haematol.2015.134049
PG 4
WC Hematology
SC Hematology
GA DQ7NA
UT WOS:000379393100007
PM 26681760
ER
PT J
AU Kepple, AL
Lee, EE
Haq, N
Rubinow, DR
Schmidt, PJ
AF Kepple, Alyson L.
Lee, Ellen E.
Haq, Nazli
Rubinow, David R.
Schmidt, Peter J.
TI History of Postpartum Depression in a Clinic-Based Sample of Women With
Premenstrual Dysphoric Disorder
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID MOOD DISORDERS; RISK-FACTORS; PERIMENOPAUSAL DEPRESSION; ANXIETY
DISORDERS; GONADAL-STEROIDS; SYMPTOMS; PREVALENCE; VULNERABILITY;
COMMUNITY; ILLNESS
AB Objective: Overlapping comorbidities between premenstrual dysphoric disorder (PMDD) and postpartum depression (PPD) suggest that these disorders represent a continuum of vulnerability with shared pathophysiology. We report the past histories of PPD (and other Axis I psychiatric illnesses) in a clinic-based sample of women meeting criteria for PMDD.
Methods: 215 women, ages 19 to 51 years, who attended the National Institute of Mental Health Mood Disorders Clinic between 1988 and 2013 seeking treatment for PMDD and in whom we confirmed the diagnosis of PMDD (DSM-IV), were identified. All were administered the Structured Clinical Interview for DSM-III-R or -IV. The frequency of PPD (major or minor) was established in the subgroup of women (n = 137) who had delivered at least 1 child.
Results: Ninety-three women (43.3%) had a past history of a mood disorder (ie, either major [n = 67; 31.2%] or minor [n = 10; 4.7%] depression or PPD [n = 16; 7.4%; 11.7% of parous women]). Nine of the 16 women with PMDD and a past PPD had either a past major depressive episode (MDE) or subsyndromal anxiety disorder. Thirty-three women (15.3%) had a past history of an Axis I anxiety disorder. A total of 40 women (18.6%) met criteria for past alcohol or drug abuse, 3 (1.4%) met criteria for bulimia nervosa, and 2 (0.9%) met criteria for anorexia nervosa.
Conclusions: Our data demonstrate that PMDD and PPD do not frequently co-occur. These data do not suggest that PMDD and PPD share similar pathophysiology beyond being ovarian-steroid-triggered mood disorders. The high comorbidity of past MDE could contribute to the increased risk both for future MDE and for PPD in some women with PMDD. (C) Copyright 2016 Physicians Postgraduate Press, Inc.
C1 [Kepple, Alyson L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA.
[Lee, Ellen E.] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA.
[Haq, Nazli; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM PeterSchmidt@mail.NIH.gov
FU National Institute of Mental Health (NIMH) [81-M-0126, MH002865]
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health (NIMH; NIMH protocol 81-M-0126;
project MH002865).
NR 49
TC 0
Z9 0
U1 9
U2 11
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD APR
PY 2016
VL 77
IS 4
BP E415
EP E420
DI 10.4088/JCP.15m09779
PG 6
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DQ5LU
UT WOS:000379247700002
PM 27035701
ER
PT J
AU Solomon, SS
Mehta, SH
McFall, AM
Srikrishnan, AK
Saravanan, S
Laeyendecker, O
Balakrishnan, P
Celentano, DD
Solomon, S
Lucas, GM
AF Solomon, Sunil Suhas
Mehta, Shruti H.
McFall, Allison M.
Srikrishnan, Aylur K.
Saravanan, Shanmugam
Laeyendecker, Oliver
Balakrishnan, Pachamuthu
Celentano, David D.
Solomon, Suniti
Lucas, Gregory M.
TI Community viral load, antiretroviral therapy coverage, and HIV incidence
in India: a cross-sectional, comparative study
SO LANCET HIV
LA English
DT Article
ID HIDDEN POPULATIONS; PREVENTION; RNA; SURVEILLANCE; INFECTION
AB Background HIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.
Methods We analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log 10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.
Findings Between Oct 1, 2012, and Dec 19, 2013, we recruited 26 503 participants, 12 022 men who have sex with men and 14 481 people who inject drugs. Median incidence of HIV was 0.87% (IQR 0.40-1.17) in men who have sex with men and 1.43% (0.60-4.00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0.81, 95% CI 0.62-0.91; p<0.0001) than all other measures, although correlation was signifi cant with aware viral load (0.59, 0.27-0.79; p=0.001), population viral load (0.51, 0.16-0.74; p=0.007), and population ART coverage (-0.54,-0.76 to -0.20; p=0.004). In-care viral load was not correlated with HIV incidence (0.29, -0.10 to 0.60; p=0.14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4.34%, and ART use in HIV-positive individuals would need to increase by 19.5%.
Interpretati on Prevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.
C1 [Solomon, Sunil Suhas; Laeyendecker, Oliver; Lucas, Gregory M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Solomon, Sunil Suhas; Mehta, Shruti H.; McFall, Allison M.; Celentano, David D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Srikrishnan, Aylur K.; Saravanan, Shanmugam; Balakrishnan, Pachamuthu; Solomon, Suniti] YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Laeyendecker, Oliver] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Solomon, SS (reprint author), Johns Hopkins Sch Med, Baltimore, MD 21287 USA.
EM sss@jhmi.edu
FU US National Institutes of Health; Elton John AIDS Foundation
FX US National Institutes of Health, Elton John AIDS Foundation.
NR 30
TC 3
Z9 3
U1 2
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 2352-3018
J9 LANCET HIV
JI Lancet HIV
PD APR
PY 2016
VL 3
IS 4
BP E183
EP E190
DI 10.1016/S2352-3018(16)00019-9
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DQ1GQ
UT WOS:000378949900011
PM 27036994
ER
PT J
AU Gill, CM
Torriani, M
Murphy, R
Harris, TB
Miller, KK
Klibanski, A
Bredella, MA
AF Gill, Corey M.
Torriani, Martin
Murphy, Rachel
Harris, Tamara B.
Miller, Karen K.
Klibanski, Anne
Bredella, Miriam A.
TI Fat Attenuation at CT in Anorexia Nervosa
SO RADIOLOGY
LA English
DT Article
ID SUBCUTANEOUS ADIPOSE-TISSUE; COMPUTED-TOMOGRAPHY; PREMENOPAUSAL WOMEN;
ABDOMINAL FAT; CANCER CACHEXIA; FEMALE-PATIENTS; WEIGHT-LOSS;
RISK-FACTOR; BODY-FAT; OBESITY
AB Purpose: To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones.
Materials and Methods: This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age 6 standard deviation, 26 years 6 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis.
Results: Women with AN had higher fat attenuation than did control subjects (-100.1 to -46.7 HU vs -117.6 to -61.8 HU, P < .0001), despite lower fat CSA (2.0-62.8 cm(2) vs 5.5-185.9 cm(2), P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = -0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = -0.34 to -0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42-0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = 20.44 to 20.58, P = .04 to .02).
Conclusion: Women with AN have differences in fat composition, with higher fat attenuation than that of control subjects, as well as low fat mass. VAT attenuation but not CSA is inversely associated with lowest prior lifetime body mass index, suggesting that fat attenuation may serve as a biomarker of prior and current disease status in AN. (C) RSNA, 2015
C1 [Gill, Corey M.; Torriani, Martin; Bredella, Miriam A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
[Miller, Karen K.; Klibanski, Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
[Murphy, Rachel; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
RP Bredella, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
EM mbredella@mgh.harvard.edu
FU National Institutes of Health [R01 MH083657, R01 DK052625, R03 DK59297,
M01 RR01066, UL1 RR025758, T32 DK 007028, K23 RR-23090]
FX This research was supported by the National Institutes of Health (grants
R01 MH083657, R01 DK052625, R03 DK59297, M01 RR01066, UL1 RR025758, T32
DK 007028, and K23 RR-23090).
NR 27
TC 0
Z9 0
U1 3
U2 4
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2016
VL 279
IS 1
BP 151
EP 157
DI 10.1148/radiol.2015151104
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DP7WK
UT WOS:000378709700014
PM 26509295
ER
PT J
AU Pourmorteza, A
Symons, R
Sandfort, V
Mallek, M
Fuld, MK
Henderson, G
Jones, EC
Malayeri, AA
Folio, LR
Bluemke, DA
AF Pourmorteza, Amir
Symons, Rolf
Sandfort, Veit
Mallek, Marissa
Fuld, Matthew K.
Henderson, Gregory
Jones, Elizabeth C.
Malayeri, Ashkan A.
Folio, Les R.
Bluemke, David A.
TI Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human
Experience
SO RADIOLOGY
LA English
DT Article
ID DUAL-ENERGY CT; DOSE REDUCTION
AB Purpose: To evaluate the performance of a prototype photon-counting detector (PCD) computed tomography (CT) system for abdominal CT in humans and to compare the results with a conventional energy-integrating detector (EID).
Materials and Methods: The study was HIPAA-compliant and institutional review board-approved with informed consent. Fifteen asymptomatic volunteers (seven men; mean age, 58.2 years +/- 9.8 [standard deviation]) were prospectively enrolled between September 2 and November 13, 2015. Radiation dose-matched delayed contrast agent-enhanced spiral and axial abdominal EID and PCD scans were acquired. Spiral images were scored for image quality (Wilcoxon signed-rank test) in five regions of interest by three radiologists blinded to the detector system, and the axial scans were used to assess Hounsfield unit accuracy in seven regions of interest (paired t test). Intraclass correlation coefficient (ICC) was used to assess reproducibility. PCD images were also used to calculate iodine concentration maps. Spatial resolution, noise-power spectrum, and Hounsfield unit accuracy of the systems were estimated by using a CT phantom.
Results: In both systems, scores were similar for image quality (median score, 4; P = .19), noise (median score, 3; P = .30), and artifact (median score, 1; P = .17), with good interrater agreement (image quality, noise, and artifact ICC: 0.84, 0.88, and 0.74, respectively). Hounsfield unit values, spatial resolution, and noise-power spectrum were also similar with the exception of mean Hounsfield unit value in the spinal canal, which was lower in the PCD than the EID images because of beam hardening (20 HU vs 36.5 HU; P < .001). Contrast-to-noise ratio of enhanced kidney tissue was improved with PCD iodine mapping compared with EID (5.2 +/- 1.3 vs 4.0 +/- 1.3; P < .001).
Conclusion: The performance of PCD showed no statistically significant difference compared with EID when the abdomen was evaluated in a conventional scan mode. PCD provides spectral information, which may be used for material decomposition. (C) RSNA, 2016
C1 [Pourmorteza, Amir; Symons, Rolf; Sandfort, Veit; Mallek, Marissa; Henderson, Gregory; Jones, Elizabeth C.; Malayeri, Ashkan A.; Folio, Les R.; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
[Fuld, Matthew K.] Siemens Med Solut, Malvern, PA USA.
RP Bluemke, DA (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM david.bluemke@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health [ZIACL090019, ZIAEB000072]
FX R.S. supported by National Institutes of Health Intramural research
program http://dx.doi.org/ (ZIACL090019; ZIAEB000072).
NR 13
TC 5
Z9 5
U1 3
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2016
VL 279
IS 1
BP 239
EP 245
DI 10.1148/radiol.2016152601
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DP7WK
UT WOS:000378709700023
PM 26840654
ER
PT J
AU Rodriguez, EK
Munasinghe, J
AF Rodriguez, Edward K.
Munasinghe, Jeeva
TI A Chick Embryo in-Vitro Model of Knee
SO ARCHIVES OF BONE AND JOINT SURGERY-ABJS
LA English
DT Article
DE chick embryo; chick embryo culture; Glycosaminoglycan; in-vitro loaded
limb culture; joint morphogenesis; paralyzed chick embryo
ID SKELETAL DEVELOPMENT; JOINT DEVELOPMENT; MOVEMENT; MORPHOGENESIS;
PARALYSIS; CARTILAGE; SYSTEM; HIP
AB Background: In this feasibility study, a mechanically loaded in-vitro tissue culture model of joint morphogenesis using the isolated lower extremity of the 8 day old chick embryo was developed to assess the effects of mechanical loading on joint morphogenesis.
Methods: The developed in-vitro system allows controlled flexion and extension of the chick embryonic knee with a range of motion of 20 degrees from a resting position of 90-100 degrees of flexion. Joint morphogenesis at 2, 3, 4 and 7 days of culture was assessed by histology and micro MRI in 4 specimen types: undisturbed in-ovo control embryos, in-ovo paralyzed embryos, in-vitro unloaded limb cultures, and in-vitro loaded limb cultures. Relative glycosaminoglycan (GAG) concentration across the joint was assessed with an MRI technique referred to as dGEMRIC (delayed gadolinium enhanced MRI of cartilage) where T1 is proportional to glycosaminoglycan concentration.
Results: Average T1 over the entire tissue image for the normal control (IC) knee was 480 msec; for the 4 day loaded specimen average T1 was 354 msec; and for the 7 day loaded specimens T1 was 393 msec. The 4 day unloaded specimen had an average T1 of 279 msec while the 7 day unloaded specimen had an average T1 of 224 msec. The higher T1 values in loaded than unloaded specimens suggest that more glycosaminoglycan is produced in the loaded culture than in the unloaded preparation.
Conclusion: Isolated limb tissue cultures under flexion-extension load can be viable and exhibit more progression of joint differentiation and glycosaminoglycan production than similarly cultured but unloaded specimens. However, when compared with controls consisting of intact undisturbed embryos in-ovo, the isolated loaded limbs in culture do not demonstrate equivalent amounts of absolute growth or joint differentiation.
C1 [Rodriguez, Edward K.; Munasinghe, Jeeva] Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA.
[Rodriguez, Edward K.] Harvard Univ, Sch Med, Orthoped Trauma Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Munasinghe, Jeeva] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Rodriguez, EK (reprint author), Harvard Univ, Sch Med, Orthoped Trauma Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
EM Ekrodrig@bidmc.harvard.edu
NR 21
TC 1
Z9 1
U1 3
U2 3
PU MASHHAD UNIV MED SCIENCES
PI MASHHAD
PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 -
445, MASHHAD, 00000, IRAN
SN 2345-4644
EI 2345-461X
J9 ARCH BONE JT SURG-AB
JI Arch. Bone Jt. Surg.-ABJS
PD APR
PY 2016
VL 4
IS 2
BP 109
EP 115
PG 7
WC Orthopedics
SC Orthopedics
GA DP7NG
UT WOS:000378685500004
PM 27200386
ER
PT J
AU Barmpari, ME
Savvidis, C
Dede, AD
Markogiannakis, H
Dikoglou, C
Xekouki, P
Stratakis, CA
Andreas, M
Malaktari-Skarantavou, S
AF Barmpari, Maria E.
Savvidis, Christos
Dede, Anastasia D.
Markogiannakis, Haridimos
Dikoglou, Christina
Xekouki, Paraskevi
Stratakis, Constantine A.
Andreas, Manouras
Malaktari-Skarantavou, Sofia
TI Adrenal malignant melanoma masquerading as a pheochromocytoma in a
patient with a history of a multifocal papillary and medullary thyroid
carcinoma
SO HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE Adrenal melanoma; Dopamine; Metastasis; Pheochromocytoma; Primary
ID FOLLOW-UP; INCIDENTALOMAS; SCINTIGRAPHY; METASTASES; MANAGEMENT;
SURVIVAL; GLANDS; TUMORS; CT
AB OBJECTIVE: Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. CASE REPORT: A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. CONCLUSION: This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.
C1 [Barmpari, Maria E.; Savvidis, Christos; Dede, Anastasia D.; Malaktari-Skarantavou, Sofia] Hippokrateion Hosp, Dept Endocrinol & Metab, Athens, Greece.
[Markogiannakis, Haridimos; Andreas, Manouras] Univ Athens, Dept Endocrine Surg, Dept Propaedeut Surg 1, Hippokrat Hosp,Athens Med Sch, GR-10679 Athens, Greece.
[Dikoglou, Christina] Hippokrateion Hosp, Dept Pathol, Athens, Greece.
[Xekouki, Paraskevi; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD USA.
RP Barmpari, ME (reprint author), 114 Vas Sofias Av, Athens 11527, Greece.
EM barbari_maria@yahoo.com
NR 35
TC 0
Z9 0
U1 0
U2 0
PU HELLENIC ENDOCRINE SOC
PI ATHENS
PA 14 ALEXANDRAS AVE, ATHENS, 106 82, GREECE
SN 1109-3099
J9 HORM-INT J ENDOCRINO
JI Horm.-Int. J. Endocrinol. Metab.
PD APR-JUN
PY 2016
VL 15
IS 2
BP 283
EP 290
DI 10.14310/horm.2002.1653
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DP9RG
UT WOS:000378833900014
PM 27376430
ER
PT J
AU Muthumani, K
Falzarano, D
Reuschel, EL
Kraynyak, K
Ugen, K
Kim, P
Maslow, J
Kim, JJ
Sardesai, NY
Kobinger, G
Feldmann, H
Weiner, D
AF Muthumani, K.
Falzarano, D.
Reuschel, E. L.
Kraynyak, K.
Ugen, K.
Kim, P.
Maslow, J.
Kim, J. J.
Sardesai, N. Y.
Kobinger, G.
Feldmann, H.
Weiner, D.
TI A synthetic consensus anti-Spike protein DNA vaccine induces protective
immunity against Middle East Respiratory Syndrome Coronavirus in
non-human primates
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Muthumani, K.; Reuschel, E. L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Falzarano, D.] Univ Saskatchewan, Saskatoon, SK, Canada.
[Kraynyak, K.; Kim, J. J.; Sardesai, N. Y.] Inovio Pharmaceut Inc, Plymouth Meeting, PA USA.
[Ugen, K.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Kim, P.; Maslow, J.] GeneOne Life Sci, Seoul, South Korea.
[Kobinger, G.] Natl Microbiol Lab, Special Pathogens, Winnipeg, MB, Canada.
[Feldmann, H.] NIAID, NIH, Hamilton, MT USA.
[Weiner, D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2016
VL 45
SU 1
MA 14.009
BP 23
EP 23
DI 10.1016/j.ijid.2016.02.083
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA DK4GZ
UT WOS:000374876700043
ER
PT J
AU Singh, N
Kumar, R
Nylen, S
Sacks, D
Sundar, S
AF Singh, N.
Kumar, R.
Nylen, S.
Sacks, D.
Sundar, S.
TI The effect of TNF-alpha neutralization on parasite load and cytokine
production in human visceral leishmaniasis
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Singh, N.] Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.
[Kumar, R.] Netaji Subhas Inst Technol, New Delhi, India.
[Nylen, S.] Karolinska Inst, Stockholm, Sweden.
[Sacks, D.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Sundar, S.] BHU, Inst Med Sci, Varanasi, Uttar Pradesh, India.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2016
VL 45
SU 1
MA 35.010
BP 62
EP 62
DI 10.1016/j.ijid.2016.02.180
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA DK4GZ
UT WOS:000374876700126
ER
PT J
AU Kharod, G
Haberling, D
Person, M
Folkema, A
Galloway, R
Elrod, M
Perniciaro, J
Nicholson, W
Patel, N
Bwogi, J
Bukenya, H
Drakeley, C
Mbulaiteye, S
Blaney, D
Shadomy, S
AF Kharod, G.
Haberling, D.
Person, M.
Folkema, A.
Galloway, R.
Elrod, M.
Perniciaro, J.
Nicholson, W.
Patel, N.
Bwogi, J.
Bukenya, H.
Drakeley, C.
Mbulaiteye, S.
Blaney, D.
Shadomy, S.
TI Uganda National Acute Febrile Illness Agent Detection Serosurvey
2004-2005
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Kharod, G.; Haberling, D.; Person, M.; Galloway, R.; Elrod, M.; Perniciaro, J.; Nicholson, W.; Patel, N.; Blaney, D.; Shadomy, S.] CDC, Atlanta, GA 30333 USA.
[Folkema, A.] CDC, Reg Waterloo Publ Hlth, Waterloo, ON, Canada.
[Bwogi, J.; Bukenya, H.] UVRI, Entebbe, Uganda.
[Drakeley, C.] Univ London London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
[Mbulaiteye, S.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2016
VL 45
SU 1
MA 41.234
BP 180
EP 180
DI 10.1016/j.ijid.2016.02.422
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA DK4GZ
UT WOS:000374876700366
ER
PT J
AU Singh, N
Kumar, R
Chauhan, SB
Nylen, S
Sacks, D
Engwerda, C
Sundar, S
AF Singh, N.
Kumar, R.
Chauhan, S. B.
Nylen, S.
Sacks, D.
Engwerda, C.
Sundar, S.
TI Investigating changes in monocyte phenotypes and functions in active
visceral leishmaniasis patients
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Singh, N.; Chauhan, S. B.; Sundar, S.] BHU, Inst Med Sci, Varanasi, Uttar Pradesh, India.
[Kumar, R.] Netaji Subhas Inst Technol, New Delhi, India.
[Nylen, S.] Karolinska Inst, Stockholm, Sweden.
[Sacks, D.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Engwerda, C.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2016
VL 45
SU 1
MA 43.076
BP 380
EP 381
DI 10.1016/j.ijid.2016.02.815
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA DK4GZ
UT WOS:000374876700759
ER
PT J
AU Virk-Baker, MK
Parascandola, M
AF Virk-Baker, Mandeep K.
Parascandola, Mark
TI Dietary adequacy in tobacco-user and non-user households in Bangladesh
SO LANCET GLOBAL HEALTH
LA English
DT Meeting Abstract
C1 [Virk-Baker, Mandeep K.] NCI, Hlth Behav Res Branch, NIH, 9609 Med Ctr Dr 3E632, Rockville, MD 20892 USA.
[Parascandola, Mark] NCI, Tobacco Control Res Branch, Behav Res Program, NIH, 9609 Med Ctr Dr 3E632, Rockville, MD 20892 USA.
EM mandeep.virk-baker@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD APR
PY 2016
VL 4
SU 1
BP 8
EP 8
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DP8DM
UT WOS:000378728100008
ER
PT J
AU Coleman, CN
Formenti, SC
Chao, N
Grover, S
Rodin, D
Petereit, DG
Vikram, B
Pistenmaa, DA
Mohiuddin, M
Williams, TR
Wendling, N
Roth, L
Gospodarowicz, M
Jaffray, D
AF Coleman, C. Norman
Formenti, Silvia C.
Chao, Nelson
Grover, Surbhi
Rodin, Danielle
Petereit, Daniel G.
Vikram, Bhadrasain
Pistenmaa, David A.
Mohiuddin, Majid
Williams, Tim R.
Wendling, Nina
Roth, Lawrence
Gospodarowicz, Mary
Jaffray, D.
TI Establishing global health cancer care partnerships across common
ground: bridging nuclear security, equitable access, education,
outreach, and mentorship
SO LANCET GLOBAL HEALTH
LA English
DT Meeting Abstract
C1 [Coleman, C. Norman; Pistenmaa, David A.; Wendling, Nina] Int Canc Expert Corps, 70 East 96th St,Suite 11A, New York, NY 10128 USA.
[Formenti, Silvia C.] Cornell Univ, Sch Med, New York, NY 10021 USA.
[Chao, Nelson] Duke Canc Inst, Durham, NC USA.
[Grover, Surbhi] Univ Penn, Philadelphia, PA 19104 USA.
[Rodin, Danielle; Gospodarowicz, Mary; Jaffray, D.] Univ Toronto, Toronto, ON, Canada.
[Petereit, Daniel G.] Amer Indian Walking Forward Program, Rapid City, SD USA.
[Vikram, Bhadrasain] NCI, Bethesda, MD 20892 USA.
[Mohiuddin, Majid] Radiat Oncol Consultants Ltd, Chicago, IL USA.
[Williams, Tim R.] Boca Raton Reg Hosp, Lynn Canc Inst, Boca Raton, FL USA.
[Gospodarowicz, Mary; Jaffray, D.] Union Int Canc Control, Task Force Radiat Canc Control, Geneva, Switzerland.
EM norm.coleman@iceccancer.org
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD APR
PY 2016
VL 4
SU 1
BP 14
EP 14
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DP8DM
UT WOS:000378728100014
ER
PT J
AU Siddharthan, T
Nassali, F
Kalyesubula, R
Coca, S
Rastegar, A
Rabin, T
Knauf, F
AF Siddharthan, Trishul
Nassali, Faith
Kalyesubula, Robert
Coca, Steve
Rastegar, Asghar
Rabin, Tracy
Knauf, Felix
TI An educational booklet for patient-centred health education about a
non-communicable disease in low-income and middle-income countries
SO LANCET GLOBAL HEALTH
LA English
DT Meeting Abstract
C1 [Siddharthan, Trishul] Johns Hopkins Univ, Baltimore, MD USA.
[Siddharthan, Trishul] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Nassali, Faith] Mulago Hosp, Kampala, Uganda.
[Kalyesubula, Robert] Makerere Univ, Kampala, Uganda.
[Coca, Steve] Ichan Sch Med Mt Sinai, New York, NY USA.
[Rastegar, Asghar; Rabin, Tracy] Yale Univ, New Haven, CT 06520 USA.
[Knauf, Felix] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany.
EM tsiddha1@jhmi.edu
NR 0
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD APR
PY 2016
VL 4
SU 1
BP 25
EP 25
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DP8DM
UT WOS:000378728100025
ER
PT J
AU Elumogo, CO
Kochenderfer, JN
Civelek, AC
Bluemke, DA
AF Elumogo, Comfort O.
Kochenderfer, James N.
Civelek, A. Cahid
Bluemke, David A.
TI Pigmented villonodular synovitis mimics metastases on fluorine 18
fluorodeoxyglucose position emission tomography-computed tomography
SO QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
LA English
DT Article
DE Pigmented villonodular synovitis (PVNS); position emission
tomography-computed tomography (PET-CT); surveillance imaging
ID LYMPHOMA; PET; CT
AB Pigmented villonodular synovitis (PVNS) is a benign joint disease best characterized on magnetic resonance imaging (MRI). The role of fluorine 18 fluorodeoxyglucose (F-18-FDG) position emission tomography-computed tomography (PET-CT) in the diagnosis or characterization remains unclear. PVNS displays as a focal FDG avid lesion, which can masquerade as a metastatic lesion, on PET-CET. We present a case of PVNS found on surveillance imaging of a lymphoma patient.
C1 [Elumogo, Comfort O.; Civelek, A. Cahid; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
OI Bluemke, David/0000-0002-8323-8086
NR 11
TC 1
Z9 1
U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2223-4292
EI 2223-4306
J9 QUANT IMAGING MED SU
JI Quant. Imaging Med. Surg.
PD APR
PY 2016
VL 6
IS 2
BP 218
EP 223
DI 10.21037/qims.2016.01.04
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DP6XT
UT WOS:000378643800015
PM 27190776
ER
PT J
AU Marks, AB
Smith, OK
Aladjem, MI
AF Marks, Anna B.
Smith, Owen K.
Aladjem, Mirit I.
TI Replication origins: determinants or consequences of nuclear
organization?
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID TOPOLOGICALLY ASSOCIATING DOMAINS; PROTEIN PHOSPHATASE 1; G-QUADRUPLEX
MOTIFS; DNA-REPLICATION; S-PHASE; MAMMALIAN-CELLS; HUMAN GENOME; C-MYC;
CHROMATIN-STRUCTURE; TRANSCRIPTIONAL CONTROL
AB Chromosome replication, gene expression and chromatin assembly all occur on the same template, necessitating a tight spatial and temporal coordination to maintain genomic stability. The distribution of replication initiation events is responsive to local and global changes in chromatin structure and is affected by transcriptional activity. Concomitantly, replication origin sequences, which determine the locations of replication initiation events, can affect chromatin structure and modulate transcriptional efficiency. The flexibility observed in the replication initiation landscape might help achieve complete and accurate genome duplication while coordinating the DNA replication program with transcription and other nuclear processes in a cell-type specific manner. This review discusses the relationships among replication origin distribution, local and global chromatin structures and concomitant nuclear metabolic processes.
C1 [Marks, Anna B.; Smith, Owen K.; Aladjem, Mirit I.] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Aladjem, MI (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM aladjemm@mail.nih.gov
FU intramural program of the CCR, National Cancer Institute, National
Institutes of Health
FX We thank Drs. Haiqing Fu and Christophe Redon for critical reading of
the review. We thank many colleagues at the NCI Developmental
Therapeutics Branch for helpful comments and apologize to our colleagues
whose primary work could not be cited due to lack of space. This work
was funded by the intramural program of the CCR, National Cancer
Institute, National Institutes of Health.
NR 91
TC 6
Z9 6
U1 3
U2 6
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD APR
PY 2016
VL 37
BP 67
EP 75
DI 10.1016/j.gde.2015.11.008
PG 9
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA DO8WX
UT WOS:000378067300010
PM 26845042
ER
PT J
AU Nix, AT
Huber, JT
Shapiro, RM
Pfeifle, A
AF Nix, A. Tyler
Huber, Jeffrey T.
Shapiro, Robert M., II
Pfeifle, Andrea
TI Examining care navigation: librarian participation in a team-based
approach?
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Article
DE Patient Navigation; Librarians; Cooperative Behavior; Delivery of Health
Care
ID PATIENT NAVIGATION; HEALTH; INFORMATION; BARRIERS; WORKERS; BREAST;
MODEL
AB Objective: This study investigated responsibilities, skill sets, degrees, and certifications required of health care navigators in order to identify areas of potential overlap with health sciences librarianship.
Method: The authors conducted a content analysis of health care navigator position announcements and developed and assigned forty-eight category terms to represent the sample's responsibilities and skill sets.
Results: Coordination of patient care and a bachelor's degree were the most common responsibility and degree requirements, respectively. Results also suggest that managing and providing health information resources is an area of overlap between health care navigators and health sciences librarians, and that librarians are well suited to serve on navigation teams.
Conclusion: Such overlap may provide an avenue for collaboration between navigators and health sciences librarians.
C1 [Nix, A. Tyler; Huber, Jeffrey T.] Univ Kentucky, Sch Informat Sci, 320 Little Lib Bldg, Lexington, KY 40506 USA.
[Shapiro, Robert M., II] Univ Kentucky, Med Ctr Lib, 298 William R Willard Med Educ Bldg, Lexington, KY 40506 USA.
[Pfeifle, Andrea] Univ Kentucky, Ctr Interprofess Healthcare Educ Res & Practice, 292 Biopharmaceut Bldg, Lexington, KY 40506 USA.
[Pfeifle, Andrea] Univ Kentucky, Family & Community Med, 292 Biopharmaceut Bldg, Lexington, KY 40506 USA.
[Nix, A. Tyler] Natl Lib Med, BG 38 RM 2N109,8600 Rockville Pike, Bethesda, MD 20894 USA.
[Pfeifle, Andrea] Indiana Univ, Ctr Interprofess Hlth Educ & Practice, 591A Gatch Hall, Indianapolis, IN 46202 USA.
[Pfeifle, Andrea] Indiana Univ, Family Med, 591A Gatch Hall, Indianapolis, IN 46202 USA.
RP Nix, AT (reprint author), Univ Kentucky, Sch Informat Sci, 320 Little Lib Bldg, Lexington, KY 40506 USA.
EM tyler.nix@uky.edu; jeffrey.huber@uky.edu; shapiro.rm@uky.edu;
andrea.pfeifle@uky.edu
OI Nix, Tyler/0000-0002-0503-386X
NR 25
TC 0
Z9 0
U1 2
U2 4
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD APR
PY 2016
VL 104
IS 2
BP 131
EP 137
DI 10.3163/1536-5050.104.2.007
PG 7
WC Information Science & Library Science
SC Information Science & Library Science
GA DP1OW
UT WOS:000378260300009
PM 27076800
ER
PT J
AU Wesolowski, A
Mensah, K
Brook, CE
Andrianjafimasy, M
Winter, A
Buckee, CO
Razafindratsimandresy, R
Tatem, AJ
Heraud, JM
Metcalf, CJE
AF Wesolowski, Amy
Mensah, Keitly
Brook, Cara E.
Andrianjafimasy, Miora
Winter, Amy
Buckee, Caroline O.
Razafindratsimandresy, Richter
Tatem, Andrew J.
Heraud, Jean-Michel
Metcalf, C. Jessica E.
TI Introduction of rubella-containing-vaccine to Madagascar: implications
for roll-out and local elimination
SO JOURNAL OF THE ROYAL SOCIETY INTERFACE
LA English
DT Article
DE rubella; vaccination; Madagascar; congenital rubella syndrome;
evaluation of vaccination programmes; Africa
ID CHILDHOOD INFECTIONS; DEVELOPING-COUNTRIES; ADDIS-ABABA; MEASLES;
DYNAMICS; EPIDEMIOLOGY; SEASONALITY; SEROEPIDEMIOLOGY; POPULATION;
CHALLENGES
AB Few countries in Africa currently include rubella-containing vaccination (RCV) in their immunization schedule. The Global Alliance for Vaccines Initiative (GAVI) recently opened a funding window that has motivated more widespread roll-out of RCV. As countries plan RCV introductions, an understanding of the existing burden, spatial patterns of vaccine coverage, and the impact of patterns of local extinction and reintroduction for rubella will be critical to developing effective programmes. As one of the first countries proposing RCV introduction in part with GAVI funding, Madagascar provides a powerful and timely case study. We analyse serological data from measles surveillance systems to characterize the epidemiology of rubella in Madagascar. Combining these results with data on measles vaccination delivery, we develop an age-structured model to simulate rubella vaccination scenarios and evaluate the dynamics of rubella and the burden of congenital rubella syndrome (CRS) across Madagascar. We additionally evaluate the drivers of spatial heterogeneity in age of infection to identify focal locations where vaccine surveillance should be strengthened and where challenges to successful vaccination introduction are expected. Our analyses indicate that characteristics of rubella in Madagascar are in line with global observations, with an average age of infection near 7 years, and an impact of frequent local extinction with reintroductions causing localized epidemics. Modelling results indicate that introduction of RCV into the routine programme alone may initially decrease rubella incidence but then result in cumulative increases in the burden of CRS in some regions (and transient increases in this burden in many regions). Deployment of RCV with regular supplementary campaigns will mitigate these outcomes. Results suggest that introduction of RCV offers a potential for elimination of rubella in Madagascar, but also emphasize both that targeted vaccination is likely to be a lynchpin of this success, and the public health vigilance that this introduction will require.
C1 [Wesolowski, Amy; Buckee, Caroline O.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wesolowski, Amy; Buckee, Caroline O.] Harvard TH Chan Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA USA.
[Mensah, Keitly; Andrianjafimasy, Miora; Razafindratsimandresy, Richter; Heraud, Jean-Michel] Inst Pasteur Madagascar, Virol Unit, Antananarivo, Madagascar.
[Mensah, Keitly; Andrianjafimasy, Miora; Razafindratsimandresy, Richter; Heraud, Jean-Michel] Inst Pasteur Madagascar, Measles & Rubella WHO Natl Reference Lab, Antananarivo, Madagascar.
[Brook, Cara E.; Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Winter, Amy; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
[Metcalf, C. Jessica E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Metcalf, C. Jessica E.] Princeton Univ, Woodrow Wilson Sch, Off Populat Res, Princeton, NJ 08544 USA.
RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.; Metcalf, CJE (reprint author), Princeton Univ, Woodrow Wilson Sch, Off Populat Res, Princeton, NJ 08544 USA.
EM cmetcalf@princeton.edu
FU James S. McDonnell Foundation; Eunice Kennedy Shriver National Institute
of Child Health and Human Development of the National Institutes of
Health [P2CHD047879]; Wellcome Trust [106866/Z/15/Z]; Princeton's Center
for Health and Wellbeing; Bill and Melinda Gates Foundation; Science and
Technology Directorate; Department of Homeland Security
[HSHQDC-12-C-00058]; RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; Models of Infectious Disease
Agent Study program [1U54GM088558]; NIH/NIAID [U19AI089674]; Bill &
Melinda Gates Foundation [OPP1106427, 1032350]
FX This work supported by the James S. McDonnell Foundation (A.
Wesolowski), the Eunice Kennedy Shriver National Institute of Child
Health and Human Development of the National Institutes of Health, grant
no. P2CHD047879 (A. Winter), a Wellcome Trust Sustaining Health grant,
no. 106866/Z/15/Z (A. Wesolowski, C.O.B., C.J.E. M. and A.J.T.), a grant
from Princeton's Center for Health and Wellbeing (C.J.E. M.), the Bill
and Melinda Gates Foundation, the Science and Technology Directorate
(C.J.E. M. and B.T.G.), Department of Homeland Security contract
HSHQDC-12-C-00058 (C.J.E. M.), the RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health (C.J.E. M., A.J.T.
and B.T.G.), the Models of Infectious Disease Agent Study program
(cooperative agreement 1U54GM088558; C.O.B., A. Wesolowski). A.J.T. is
supported by funding from NIH/NIAID (U19AI089674), the Bill & Melinda
Gates Foundation (OPP1106427, 1032350).
NR 43
TC 0
Z9 0
U1 3
U2 3
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD APR 1
PY 2016
VL 13
IS 117
AR 20151101
DI 10.1098/rsif.2015.1101
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP2IM
UT WOS:000378311800007
ER
PT J
AU Bourhy, H
Nakoune, E
Hall, M
Nouvellet, P
Lepelletier, A
Talbi, C
Watier, L
Holmes, EC
Cauchemez, S
Lemey, P
Donnelly, CA
Rambaut, A
AF Bourhy, Herve
Nakoune, Emmanuel
Hall, Matthew
Nouvellet, Pierre
Lepelletier, Anthony
Talbi, Chiraz
Watier, Laurence
Holmes, Edward C.
Cauchemez, Simon
Lemey, Philippe
Donnelly, Christl A.
Rambaut, Andrew
TI Revealing the Micro-scale Signature of Endemic Zoonotic Disease
Transmission in an African Urban Setting
SO PLOS PATHOGENS
LA English
DT Article
ID DOG RABIES VIRUS; METAPOPULATION DYNAMICS; IDENTIFYING RESERVOIRS;
PHYLOGENETIC ANALYSIS; REPRODUCTION NUMBERS; POPULATION-DYNAMICS;
INFECTIOUS-DISEASES; CANINE RABIES; ELIMINATION; EPIDEMIC
AB The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui.
C1 [Bourhy, Herve; Lepelletier, Anthony; Talbi, Chiraz] WHO Collaborating Ctr Reference & Res Rabies, Unit Lyssavirus Dynam & Host Adaptat, Inst Pasteur, Paris, France.
[Nakoune, Emmanuel] Inst Pasteur, Bangui, Cent Afr Republ.
[Hall, Matthew; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland.
[Hall, Matthew; Nouvellet, Pierre; Cauchemez, Simon; Donnelly, Christl A.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England.
[Nouvellet, Pierre; Cauchemez, Simon; Donnelly, Christl A.] Univ London Imperial Coll Sci Technol & Med, Med Res Council, Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England.
[Watier, Laurence] INSERM, UMR 1181, Paris, France.
[Watier, Laurence] Inst Pasteur, B2PHI, Paris, France.
[Watier, Laurence] Univ Versailles St Quentin, Fac Med Paris Ile France Ouest, Versailles, France.
[Holmes, Edward C.] Sch Life & Environm Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW, Australia.
[Holmes, Edward C.] Sydney Med Sch, Sydney, NSW, Australia.
[Cauchemez, Simon] Inst Pasteur, Math Modelling Infect Dis Unit, Paris, France.
[Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Leuven, Belgium.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Bourhy, H (reprint author), WHO Collaborating Ctr Reference & Res Rabies, Unit Lyssavirus Dynam & Host Adaptat, Inst Pasteur, Paris, France.
EM hbourhy@pasteur.fr
RI Watier, Laurence/K-8213-2013;
OI Watier, Laurence/0000-0002-4057-1102; Holmes, Edward/0000-0001-9596-3552
FU European Union Seventh Framework Programme PREDEMICS [278433]; NHMRC
Australia Fellowship
FX This work was supported by European Union Seventh Framework Programme
PREDEMICS (grant number 278433). ECH is supported by an NHMRC Australia
Fellowship. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 53
TC 2
Z9 2
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD APR
PY 2016
VL 12
IS 4
AR e1005525
DI 10.1371/journal.ppat.1005525
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0CZ
UT WOS:000378156900021
PM 27058957
ER
PT J
AU Buck, CB
Van Doorslaer, K
Peretti, A
Geoghegan, EM
Tisza, MJ
An, P
Katz, JP
Pipas, JM
McBride, AA
Camus, AC
McDermott, AJ
Dill, JA
Delwart, E
Ng, TFF
Farkas, K
Austin, C
Kraberger, S
Davison, W
Pastrana, DV
Varsani, A
AF Buck, Christopher B.
Van Doorslaer, Koenraad
Peretti, Alberto
Geoghegan, Eileen M.
Tisza, Michael J.
An, Ping
Katz, Joshua P.
Pipas, James M.
McBride, Alison A.
Camus, Alvin C.
McDermott, Alexa J.
Dill, Jennifer A.
Delwart, Eric
Ng, Terry F. F.
Farkas, Kata
Austin, Charlotte
Kraberger, Simona
Davison, William
Pastrana, Diana V.
Varsani, Arvind
TI The Ancient Evolutionary History of Polyomaviruses
SO PLOS PATHOGENS
LA English
DT Article
ID MERKEL CELL POLYOMAVIRUS; GOOSE HEMORRHAGIC POLYOMAVIRUS; MULTIPLE
SEQUENCE ALIGNMENT; LARGE T-ANTIGEN; AVIAN POLYOMAVIRUS; MOLECULAR
PHYLOGENY; PYGOSCELIS-ADELIAE; DIVERGENCE TIMES; MIDDLE T; VIRUS
AB Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae.
C1 [Buck, Christopher B.; Peretti, Alberto; Geoghegan, Eileen M.; Tisza, Michael J.; Pastrana, Diana V.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Van Doorslaer, Koenraad; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[An, Ping; Katz, Joshua P.; Pipas, James M.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Camus, Alvin C.; Dill, Jennifer A.] Univ Georgia, Dept Pathol, Athens, GA 30602 USA.
[McDermott, Alexa J.] Georgia Aquarium Inc, Dept Anim Hlth, Atlanta, GA USA.
[Delwart, Eric; Ng, Terry F. F.] Blood Syst Res Inst, San Francisco, CA USA.
[Delwart, Eric; Ng, Terry F. F.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Farkas, Kata; Austin, Charlotte; Kraberger, Simona; Davison, William; Varsani, Arvind] Univ Canterbury, Sch Biol Sci, Christchurch 1, New Zealand.
[Varsani, Arvind] Univ Cape Town, Dept Clin Lab Sci, Struct Biol Res Unit, ZA-7925 Cape Town, South Africa.
[Varsani, Arvind] Univ Florida, Dept Plant Pathol, Gainesville, FL 32611 USA.
[Varsani, Arvind] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Ng, Terry F. F.] Ctr Dis Control, DVD, NCIRD, Atlanta, GA 30333 USA.
RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
EM buckc@mail.nih.gov
OI Van Doorslaer, Koenraad/0000-0002-2985-0733; Ng, Terry Fei
Fan/0000-0002-4815-8697; McBride, Alison/0000-0001-5607-5157
FU National Institutes of Health; National Cancer Institute Center for
Cancer Research; National Institute of Allergy and Infectious Disease;
Antarctica New Zealand [K057]; National Institute of Allergy and
Infectious Diseases [AI109339]; Italian Foundation for Cancer Research
(FIRC)
FX This work was funded in part by the National Institutes of Health
Intramural Research Program, with support from the National Cancer
Institute Center for Cancer Research. AAM and KVD were funded by the
Intramural Research Program of the National Institute of Allergy and
Infectious Disease. Trematomus pennellii were collected in the Antarctic
under the 2011/08R animal ethics permit and the field work was supported
by a grant (K057) awarded to WD from Antarctica New Zealand. The
Trematomus pennelli molecular work was supported by personal funds of
AV. The structural analyses for the large T antigens by PA, JPK and JMP
were supported by an R21 grant AI109339 awarded to JMP by National
Institute of Allergy and Infectious Diseases. AP is supported by a grant
from the Italian Foundation for Cancer Research (FIRC). Aside from the
contribution of personal funds by AV, other funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 103
TC 6
Z9 6
U1 3
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD APR
PY 2016
VL 12
IS 4
AR e1005574
DI 10.1371/journal.ppat.1005574
PG 26
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0CZ
UT WOS:000378156900052
PM 27093155
ER
PT J
AU Carroll, JA
Striebel, JF
Rangel, A
Woods, T
Phillips, K
Peterson, KE
Race, B
Chesebro, B
AF Carroll, James A.
Striebel, James F.
Rangel, Alejandra
Woods, Tyson
Phillips, Katie
Peterson, Karin E.
Race, Brent
Chesebro, Bruce
TI Prion Strain Differences in Accumulation of PrPSc on Neurons and Glia
Are Associated with Similar Expression Profiles of Neuroinflammatory
Genes: Comparison of Three Prion Strains
SO PLOS PATHOGENS
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; SCRAPIE-INFECTED MICE; INDUCED NEUROLOGICAL
DISEASE; MURINE RETROVIRUS; DNA MICROARRAY; MOUSE SCRAPIE; AGENT-STRAIN;
PROTEIN; PATHOGENESIS; BRAIN
AB Misfolding and aggregation of host proteins are important features of the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, frontotemporal dementia and prion diseases. In all these diseases, the misfolded protein increases in amount by a mechanism involving seeded polymerization. In prion diseases, host prion protein is misfolded to form a pathogenic protease-resistant form, PrPSc, which accumulates in neurons, astroglia and microglia in the CNS. Here using dual-staining immunohistochemistry, we compared the cell specificity of PrPSc accumulation at early preclinical times post-infection using three mouse scrapie strains that differ in brain regional pathology. PrPSc from each strain had a different pattern of cell specificity. Strain 22L was mainly associated with astroglia, whereas strain ME7 was mainly associated with neurons and neuropil. In thalamus and cortex, strain RML was similar to 22L, but in substantia nigra, RML was similar to ME7. Expression of 90 genes involved in neuroinflammation was studied quantitatively using mRNA from thalamus at preclinical times. Surprisingly, despite the cellular differences in PrPSc accumulation, the pattern of upregulated genes was similar for all three strains, and the small differences observed correlated with variations in the early disease tempo. Gene upregulation correlated with activation of both astroglia and microglia detected in early disease prior to vacuolar pathology or clinical signs. Interestingly, the profile of upregulated genes in scrapie differed markedly from that seen in two acute viral CNS diseases (LaCrosse virus and BE polytropic Friend retrovirus) that had reactive gliosis at levels similar to our prion-infected mice.
C1 [Carroll, James A.; Striebel, James F.; Rangel, Alejandra; Woods, Tyson; Phillips, Katie; Peterson, Karin E.; Race, Brent; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Rangel, Alejandra] Univ Western Sydney, Pharmacol, Campbelltown, NSW, Australia.
RP Chesebro, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM bchesebro@nih.gov
FU National Institute of Allergy and Infectious Diseases, Division of
Intramural Research
FX This work was supported by the National Institute of Allergy and
Infectious Diseases, Division of Intramural Research. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 71
TC 1
Z9 1
U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD APR
PY 2016
VL 12
IS 4
AR e1005551
DI 10.1371/journal.ppat.1005551
PG 26
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0CZ
UT WOS:000378156900035
PM 27046083
ER
PT J
AU Mason, RD
Welles, HC
Adams, C
Chakrabarti, BK
Gorman, J
Zhou, TQ
Nguyen, R
O'Dell, S
Lusvarghi, S
Bewley, CA
Li, H
Shaw, GM
Sheng, ZZ
Shapiro, L
Wyatt, R
Kwong, PD
Mascola, JR
Roederer, M
AF Mason, Rosemarie D.
Welles, Hugh C.
Adams, Cameron
Chakrabarti, Bimal K.
Gorman, Jason
Zhou, Tongqing
Nguyen, Richard
O'Dell, Sijy
Lusvarghi, Sabrina
Bewley, Carole A.
Li, Hui
Shaw, George M.
Sheng, Zizhang
Shapiro, Lawrence
Wyatt, Richard
Kwong, Peter D.
Mascola, John R.
Roederer, Mario
TI Targeted Isolation of Antibodies Directed against Major Sites of SIV Env
Vulnerability
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; BROADLY NEUTRALIZING ANTIBODIES; RHESUS
MONOCLONAL-ANTIBODIES; POTENT HIV-1 NEUTRALIZATION; ENVELOPE
GLYCOPROTEINS; CYANOVIRIN-N; SHIV CHALLENGE; NONNEUTRALIZING ANTIBODIES;
MOLECULAR CHARACTERIZATION; CONFORMATIONAL-CHANGES
AB The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-2(7312A). This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy.
C1 [Mason, Rosemarie D.; Welles, Hugh C.; Adams, Cameron; Gorman, Jason; Zhou, Tongqing; Nguyen, Richard; O'Dell, Sijy; Kwong, Peter D.; Mascola, John R.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Chakrabarti, Bimal K.] Translat Hlth Sci & Technol Inst, IAVI, HIV Vaccine Design Program, Pali, Haryana, India.
[Lusvarghi, Sabrina; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Li, Hui; Shaw, George M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Li, Hui; Shaw, George M.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Sheng, Zizhang; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
[Sheng, Zizhang; Shapiro, Lawrence] Columbia Univ, Dept Syst Biol, New York, NY USA.
[Wyatt, Richard] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
RP Mason, RD; Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rosemarie.mason@nih.gov; marior@mail.nih.gov
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU Vaccine Research Center, NIAID, NIH; NIDDK, NIH; National Institutes of
Health (NIH) [P01 AI088564]
FX This work was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID, NIH and the Intramural Research Program
of NIDDK, NIH. HL and GMS were supported in part by a grant from the
National Institutes of Health (NIH P01 AI088564). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 112
TC 4
Z9 4
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD APR
PY 2016
VL 12
IS 4
AR e1005537
DI 10.1371/journal.ppat.1005537
PG 33
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0CZ
UT WOS:000378156900027
PM 27064278
ER
PT J
AU Utay, NS
Roque, A
Timmer, JK
Morcock, DR
DeLeage, C
Somasunderam, A
Weintrob, AC
Agan, BK
Estes, JD
Crum-Cianflone, NF
Douek, DC
AF Utay, Netanya S.
Roque, Annelys
Timmer, J. Katherina
Morcock, David R.
DeLeage, Claire
Somasunderam, Anoma
Weintrob, Amy C.
Agan, Brian K.
Estes, Jacob D.
Crum-Cianflone, Nancy F.
Douek, Daniel C.
TI MRSA Infections in HIV-Infected People Are Associated with Decreased
MRSA-Specific Th1 Immunity
SO PLOS PATHOGENS
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; HERPES-SIMPLEX-VIRUS; HYPER-IGE
SYNDROME; GAMMA-INTERFERON; T-CELLS; ANTIRETROVIRAL THERAPY; IFN-GAMMA;
DEFICIENCY; INTERLEUKIN-2; ZOSTER
AB People with HIV infection are at increased risk for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs). Lower CD4 T-cell counts, higher peak HIV RNA levels and epidemiological factors may be associated with increased risk but no specific immune defect has been identified. We aimed to determine the immunologic perturbations that predispose HIV-infected people to MRSA SSTIs. Participants with or without HIV infection and with MRSA SSTI, MRSA colonization or negative for MRSA were enrolled. Peripheral blood and skin biopsies from study participants were collected. Flow cytometry, flow cytometry with microscopy, multiplex assays of cell culture supernatants and immunohistochemistry were used to evaluate the nature of the immune defect predisposing HIV-infected people to MRSA infections. We found deficient MRSA-specific IFN gamma(+) CD4 T-cell responses in HIV-infected people with MRSA SSTIs compared to MRSA-colonized participants and HIV-uninfected participants with MRSA SSTIs. These IFN gamma(+) CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs. However, IFN gamma responses to cytomegalovirus and Mycobacterium avium antigens and MRSA-specific IL-17 responses by CD4 T cells were intact. Upon stimulation with MRSA, peripheral blood mononuclear cells from HIV-infected participants produced less IL-12 and IL-15, key drivers of IFN gamma production. There were no defects in CD8 T-cell responses, monocyte responses, opsonization, or phagocytosis of Staphylococcus aureus. Accumulation of CD3 T cells, CD4 T cells, IL-17(+) cells, myeloperoxidase(+) neutrophils and macrophage/myeloid cells to the skin lesions were similar between HIV-infected and HIV-uninfected participants based on immunohistochemistry. Together, these results indicate that MRSA-specific IFN gamma(+) CD4 T-cell responses are essential for the control of initial and recurrent MRSA infections in HIV-infected people.
C1 [Utay, Netanya S.; Somasunderam, Anoma] Univ Texas Med Branch, Dept Internal Med, Div Infect Dis, Galveston, TX 77555 USA.
[Roque, Annelys; Timmer, J. Katherina; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Morcock, David R.; DeLeage, Claire; Estes, Jacob D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Weintrob, Amy C.; Agan, Brian K.; Crum-Cianflone, Nancy F.] Uniformed Serv Univ Hlth Sci, IDCRP, Dept Prevent Med & Biostat, Bethesda, MD 20814 USA.
[Weintrob, Amy C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Agan, Brian K.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Crum-Cianflone, Nancy F.] Naval Med Ctr San Diego, Infect Dis Clin, San Diego, CA USA.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
OI Agan, Brian/0000-0002-5114-1669
FU Infectious Disease Clinical Research Program, a Department of Defense
[IDCRP-023]; National Institute of Allergy and Infectious
Diseases/National Institutes of Health [Y1-AI-5072]; National Cancer
Institute/National Institutes of Health [HHSN261200800001E]
FX Support for this work (IDCRP-023) was provided by Infectious Disease
Clinical Research Program, a Department of Defense program executed
through Uniformed Services University of the Health Sciences and in part
by National Institute of Allergy and Infectious Diseases/National
Institutes of Health, under Inter-Agency Agreement Y1-AI-5072, and
National Cancer Institute/National Institutes of Health, under Contract
No. HHSN261200800001E. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 31
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD APR
PY 2016
VL 12
IS 4
AR e1005580
DI 10.1371/journal.ppat.1005580
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0CZ
UT WOS:000378156900056
PM 27093273
ER
PT J
AU Faulkner, LM
Kisser, J
Waldstein, SR
Sutin, AR
Evans, MK
Zonderman, AB
AF Faulkner, Lauren M.
Kisser, Jason
Waldstein, Shari R.
Sutin, Angelina R.
Evans, Michele K.
Zonderman, Alan B.
TI EFFECTS OF EMOTIONAL SUPPORT ON COGNITIVE PERFORMANCE MAY BE MODERATED
BY PERSONALITY FACTORS
SO PSYCHOSOMATIC MEDICINE
LA English
DT Meeting Abstract
CT 74th Annual Meeting of the American-Psychosomatic-Society
CY MAR 09-12, 2015
CL Denver, CO
SP Amer Psychosomat Soc
C1 [Faulkner, Lauren M.; Kisser, Jason; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Psychol, Baltimore, MD 21228 USA.
[Sutin, Angelina R.] Florida State Univ, Behav Sci & Social Med, Tallahassee, FL 32306 USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, NIH, Baltimore, MD 21224 USA.
[Zonderman, Alan B.] NIA, Behav Epidemiol Sect, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD APR
PY 2016
VL 78
IS 3
MA 1475
BP A121
EP A121
PG 1
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DJ1FX
UT WOS:000373949800393
ER
PT J
AU Leibel, DK
Waldstein, SR
Evans, MK
Zonderman, AB
AF Leibel, Daniel K.
Waldstein, Shari R.
Evans, Michele K.
Zonderman, Alan B.
TI INTERACTIVE RELATIONS OF AGE, SEX, RACE, AND POVERTY STATUS TO PHYSICAL
FUNCTIONING IN AN URBAN-DWELLING SAMPLE OF ADULTS
SO PSYCHOSOMATIC MEDICINE
LA English
DT Meeting Abstract
CT 74th Annual Meeting of the American-Psychosomatic-Society
CY MAR 09-12, 2015
CL Denver, CO
SP Amer Psychosomat Soc
C1 [Leibel, Daniel K.; Waldstein, Shari R.] Univ Maryland, Psychol, Baltimore, MD 21201 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD APR
PY 2016
VL 78
IS 3
MA 1264
BP A136
EP A136
PG 1
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DJ1FX
UT WOS:000373949800440
ER
PT J
AU Loucks, EB
Gilman, SE
Britton, WB
Gutman, R
Eaton, CB
Buka, SL
AF Loucks, Eric B.
Gilman, Stephen E.
Britton, Willoughby B.
Gutman, Roee
Eaton, Charles B.
Buka, Stephen L.
TI ASSOCIATIONS OF MINDFULNESS WITH GLUCOSE REGULATION AND DIABETES: NEW
ENGLAND FAMILY STUDY
SO PSYCHOSOMATIC MEDICINE
LA English
DT Meeting Abstract
CT 74th Annual Meeting of the American-Psychosomatic-Society
CY MAR 09-12, 2015
CL Denver, CO
SP Amer Psychosomat Soc
C1 [Loucks, Eric B.; Buka, Stephen L.] Brown Univ, Sch Publ Hlth, Epidemiol, Providence, RI 02912 USA.
[Gilman, Stephen E.] NICHHD, Hlth Behav Branch, Washington, DC USA.
[Britton, Willoughby B.] Brown Univ, Psychiat, Providence, RI 02912 USA.
[Gutman, Roee] Brown Univ, Sch Publ Hlth, Biostat, Providence, RI 02912 USA.
[Eaton, Charles B.] Brown Univ, Family Med, Providence, RI 02912 USA.
NR 0
TC 0
Z9 0
U1 9
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD APR
PY 2016
VL 78
IS 3
MA 1258
BP A76
EP A76
PG 1
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DJ1FX
UT WOS:000373949800235
ER
PT J
AU Lovallo, WR
Enoch, MA
Acheson, A
Cohoon, AJ
Sorocco, KH
Vincent, AS
Goldman, D
AF Lovallo, William R.
Enoch, Mary-Anne
Acheson, Ashley
Cohoon, Andrew J.
Sorocco, Kristen H.
Vincent, Andrea S.
Goldman, David
TI EARLY-LIFE ADVERSITY INTERACTS WITH FKBP5 GENOTYPES: GENE-BY-ENVIRONMENT
INTERACTION IN THE OKLAHOMA FAMILY HEALTH PATTERNS PROJECT
SO PSYCHOSOMATIC MEDICINE
LA English
DT Meeting Abstract
CT 74th Annual Meeting of the American-Psychosomatic-Society
CY MAR 09-12, 2015
CL Denver, CO
SP Amer Psychosomat Soc
C1 [Lovallo, William R.] VA Med Ctr, Psychiat & Behav Sci, Oklahoma City, OK USA.
[Lovallo, William R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Enoch, Mary-Anne; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
[Acheson, Ashley] Univ Texas Hlth Sci Ctr San Antonio, Psychiat, San Antonio, TX 78229 USA.
[Cohoon, Andrew J.] Univ Oklahoma, Hlth Sci Ctr, Psychiat & Behav Sci, Oklahoma City, OK USA.
[Sorocco, Kristen H.] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK USA.
[Vincent, Andrea S.] Univ Oklahoma, Cognit Sci Res Ctr, Norman, OK 73019 USA.
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Department of Veterans Affairs; NIH, NIAAA [AA12207]
FX Supported by the Department of Veterans Affairs and NIH, NIAAA AA12207
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD APR
PY 2016
VL 78
IS 3
MA 1166
BP A30
EP A30
PG 1
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DJ1FX
UT WOS:000373949800095
ER
PT J
AU Taylor, AD
Agurs-Collins, T
Persoskie, A
Perna, F
AF Taylor, Antione D.
Agurs-Collins, Tanya
Persoskie, Alexander
Perna, Frank
TI BMI AS A MEDIATOR IN THE RELATION OF DISCRIMINATION AND INFLAMMATION
SO PSYCHOSOMATIC MEDICINE
LA English
DT Meeting Abstract
CT 74th Annual Meeting of the American-Psychosomatic-Society
CY MAR 09-12, 2015
CL Denver, CO
SP Amer Psychosomat Soc
C1 [Taylor, Antione D.] Univ Maryland Baltimore Cty, Psychol, Baltimore, MD 21228 USA.
[Agurs-Collins, Tanya; Perna, Frank] NCI, Behav Res Program, Rockville, MD USA.
[Persoskie, Alexander] US FDA, Populat Hlth Sci Ctr Tobacco Prod, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD APR
PY 2016
VL 78
IS 3
MA 1125
BP A88
EP A88
PG 1
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DJ1FX
UT WOS:000373949800278
ER
PT J
AU Xiao, Q
Signorello, LB
Brinton, LA
Cohen, SS
Blot, WJ
Matthews, CE
AF Xiao, Qian
Signorello, Lisa B.
Brinton, Louise A.
Cohen, Sarah S.
Blot, William J.
Matthews, Charles E.
TI Sleep duration and breast cancer risk among black and white women
SO SLEEP MEDICINE
LA English
DT Article
DE Sleep; Breast cancer; Black women; Hormone receptor-positive breast
cancer; Hormone receptor-negative breast cancer
ID URINARY MELATONIN LEVELS; CHINESE WOMEN; COHORT; SINGAPORE; NURSES;
HEALTH; US
AB Background: Sleep has been suggested to influence breast cancer risk; however, the evidence is mixed. Black women have a higher prevalence of both short (<6 h) and long (>= 9 h) sleep duration and are more likely to develop more aggressive, hormone receptor-negative breast cancer. No study has examined the relationship between sleep and breast cancer in blacks. We focused on race-specific associations among the blacks.
Methods: In the Southern Community Cohort Study (SCCS), a prospective study of which two-thirds of the population were black, we prospectively investigated self-reported sleep duration in relation to overall breast cancer risk by estrogen (ER) and progesterone receptor (PR) status in all women and in black women alone.
Results: Sleep duration was not associated with risk of total or hormone receptor-positive breast cancer. However, we found an inverse relationship between sleep duration and risk of ER- and PR-breast cancer among all women and in black women alone. Compared to the reference group (8 h), black women who reported shorter sleep duration had an increased risk of ER-PR-breast cancer (odds ratios; ORs (95% confidence intervals; CIs): 2.13 (1.15, 3.93), 1.66 (0.92, 3.02), and 2.22 (1.19, 4.12) for <6, 6, and 7 h, respectively, (p for trend, 0.04).
Conclusions: Short sleep duration may be a risk factor for hormone receptor-negative breast cancer among black women. Published by Elsevier B.V.
C1 [Xiao, Qian; Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Signorello, Lisa B.] NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Cohen, Sarah S.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Blot, William J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
RP Xiao, Q (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM qian.xiao@nih.gov
FU Intramural Research Program of National Institutes of Health; National
Cancer Institute, National Institutes of Health; Department of Health
and Human Services
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services.
NR 25
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD APR
PY 2016
VL 20
BP 25
EP 29
DI 10.1016/j.sleep.2015.11.010
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DO8RO
UT WOS:000378051400005
PM 27318222
ER
PT J
AU Sharov, A
Maran, T
Tonnessen, M
AF Sharov, Alexei
Maran, Timo
Tonnessen, Morten
TI Comprehending the Semiosis of Evolution
SO BIOSEMIOTICS
LA English
DT Editorial Material
C1 [Sharov, Alexei] NIA, Lab Genet & Genom, Baltimore, MD 21224 USA.
[Maran, Timo] Univ Tartu, Dept Semiot, Ulikooli 18, EE-50090 Tartu, Estonia.
[Tonnessen, Morten] Univ Stavanger, Dept Social Studies, Stavanger, Norway.
[Tonnessen, Morten] Univ Stavanger, Dept Hlth Studies, Stavanger, Norway.
RP Sharov, A (reprint author), NIA, Lab Genet & Genom, Baltimore, MD 21224 USA.
EM sharoval@mail.nih.gov
FU National Institute on Aging (NIA/NIH)
FX The contribution of A. S. was supported entirely by the Intramural
Research Program of the National Institute on Aging (NIA/NIH).
NR 12
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1875-1342
EI 1875-1350
J9 BIOSEMIOTICS-NETH
JI Biosemiotics
PD APR
PY 2016
VL 9
IS 1
BP 1
EP 6
DI 10.1007/s12304-016-9262-7
PG 6
WC Humanities, Multidisciplinary; History & Philosophy Of Science
SC Arts & Humanities - Other Topics; History & Philosophy of Science
GA DO5FD
UT WOS:000377808100001
PM 27547273
ER
PT J
AU Sharov, AA
AF Sharov, Alexei A.
TI Evolution of Natural Agents: Preservation, Advance, and Emergence of
Functional Information
SO BIOSEMIOTICS
LA English
DT Article
DE Extended evolutionary synthesis; Epigenetic inheritance; Inclusive
heritability; Selective reproduction; Plasticity; Levels of semiosis
ID BIOLOGY; ORIGIN; BIOSEMIOTICS; FEATHERS; LIFE
AB Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs (e.g., memory, transient messengers, and external signs) that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via complex interplay of copying and construction processes: the digital components are copied, whereas interpreting subagents together with scaffolds, tools, and resources, are constructed. Some of these processes are simple and invariant, whereas others are complex and contextual. Advance of functional information includes improvement and modification of already existing functions. Although the genome information may change passively and randomly, the interpretation is active and guided by the logic of agent behavior and embryonic development. Emergence of new functions is based on the reinterpretation of already existing information, when old tools, resources, and control algorithms are adopted for novel functions. Evolution of functional information progressed from protosemiosis, where signs correspond directly to actions, to eusemiosis, where agents associate signs with objects. Language is the most advanced form of eusemiosis, where the knowledge of objects and models is communicated between agents.
C1 [Sharov, Alexei A.] NIA, Lab Genet & Gen, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Sharov, AA (reprint author), NIA, Lab Genet & Gen, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sharoval@grc.nia.nih.gov
FU National Institute on Aging (NIA/NIH) [ZIA AG000656-13]
FX This research was supported entirely by the Intramural Research Program
of the National Institute on Aging (NIA/NIH), project ZIA AG000656-13.
The content of the paper is not endorsed or suggested by the funding
organization.
NR 63
TC 1
Z9 1
U1 4
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1875-1342
EI 1875-1350
J9 BIOSEMIOTICS-NETH
JI Biosemiotics
PD APR
PY 2016
VL 9
IS 1
BP 103
EP 120
DI 10.1007/s12304-015-9250-3
PG 18
WC Humanities, Multidisciplinary; History & Philosophy Of Science
SC Arts & Humanities - Other Topics; History & Philosophy of Science
GA DO5FD
UT WOS:000377808100008
PM 27525048
ER
PT J
AU Taichman, CDB
Backus, J
Baethge, C
Bauchner, H
de Leeuwe, PW
Drazen, JM
Fletcher, J
Frizelle, FA
Groves, T
Haileamlak, A
James, A
Laine, C
Peiperl, L
Pinborg, A
Sahni, CP
Wu, S
AF Taichman, C. Darren B.
Backus, Joyce
Baethge, Christopher
Bauchner, Howard
de Leeuwe, Peter W.
Drazen, Jeffrey M.
Fletcher, John
Frizelle, Frank A.
Groves, Trish
Haileamlak, Abraham
James, Astrid
Laine, Christine
Peiperl, Larry
Pinborg, Anja
Sahni, C. Peush
Wu, Sinan
TI Sharing Clinical Trial Data - A Proposal from the International
Committee of Medical Journal Editors
SO CORSALUD
LA Spanish
DT Editorial Material
DE Clinical trial; Research data; Medical journal; Editors
C1 [Taichman, C. Darren B.] ICMJE, Philadelphia, PA USA.
[Backus, Joyce] Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA.
RP Taichman, CDB (reprint author), Amer Coll Physicians, Int Comm Med Journal Editors, 190 N Independence Mall West, Philadelphia, PA 19106 USA.
EM dtaichman@acponline.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU CARDIOCENTRO ERNESTO CHE GUEVARA
PI VILLA CLARA
PA CALLE CUBA 610, E-BARCELONA & CAPITAN VELAZCO, SANTA CLARA, VILLA CLARA,
CP 50200, CUBA
SN 2078-7170
J9 CORSALUD
JI CorSalud
PD APR-JUN
PY 2016
VL 8
IS 2
BP 88
EP 91
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO7ZY
UT WOS:000378003000001
ER
PT J
AU Daly, AF
Yuan, B
Fina, F
Caberg, JH
Trivellin, G
Rostomyan, L
de Herder, WW
Naves, LA
Metzger, D
Cuny, T
Rabl, W
Shah, N
Jaffrain-Rea, ML
Zatelli, MC
Faucz, FR
Castermans, E
Nanni-Metellus, I
Lodish, M
Muhammad, A
Palmeira, L
Potorac, I
Mantovani, G
Neggers, SJ
Klein, M
Barlier, A
Liu, PF
Ouafik, L
Bours, V
Lupski, JR
Stratakis, CA
Beckers, A
AF Daly, Adrian F.
Yuan, Bo
Fina, Frederic
Caberg, Jean-Hubert
Trivellin, Giampaolo
Rostomyan, Liliya
de Herder, Wouter W.
Naves, Luciana A.
Metzger, Daniel
Cuny, Thomas
Rabl, Wolfgang
Shah, Nalini
Jaffrain-Rea, Marie-Lise
Zatelli, Maria Chiara
Faucz, Fabio R.
Castermans, Emilie
Nanni-Metellus, Isabelle
Lodish, Maya
Muhammad, Ammar
Palmeira, Leonor
Potorac, Iulia
Mantovani, Giovanna
Neggers, Sebastian J.
Klein, Marc
Barlier, Anne
Liu, Pengfei
Ouafik, L'Houcine
Bours, Vincent
Lupski, James R.
Stratakis, Constantine A.
Beckers, Albert
TI Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic
male subjects
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE X-LAG syndrome; mosaicism; gigantism; pituitary; molecular genetics
ID MCCUNE-ALBRIGHT-SYNDROME; DE-LANGE-SYNDROME; GENOMIC DISORDERS;
COPY-NUMBER; TRANSMISSION GENETICS; ACTIVATING MUTATION;
PITUITARY-ADENOMAS; GERMLINE MUTATION; RECURRENCE RISK; ARRAY CGH
AB Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101. We studied XLAG syndrome patients (n = 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2 ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes.
C1 [Daly, Adrian F.; Rostomyan, Liliya; Palmeira, Leonor; Potorac, Iulia; Beckers, Albert] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, Liege, Belgium.
[Yuan, Bo; Liu, Pengfei; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Fina, Frederic; Nanni-Metellus, Isabelle] Hop Nord Marseille, AP HM, Serv Transfert Oncol Biol, Marseille, France.
[Fina, Frederic; Ouafik, L'Houcine] Lab Biol Med, Marseille, France.
[Fina, Frederic; Ouafik, L'Houcine] Aix Marseille Univ, INSERM, CRO2 UMR S 911, Marseille, France.
[Caberg, Jean-Hubert; Castermans, Emilie; Potorac, Iulia; Bours, Vincent] Univ Liege, Ctr Hosp Univ Liege, Dept Human Genet, Liege, Belgium.
[Trivellin, Giampaolo; Faucz, Fabio R.; Lodish, Maya; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[de Herder, Wouter W.; Muhammad, Ammar; Neggers, Sebastian J.] Erasmus Univ, Med Ctr Rotterdam, Dept Med, Sect Endocrinol, Rotterdam, Netherlands.
[de Herder, Wouter W.; Muhammad, Ammar; Neggers, Sebastian J.] Pituitary Ctr Rotterdam, Rotterdam, Netherlands.
[Naves, Luciana A.] Univ Brasilia, Dept Endocrinol, Brasilia, DF, Brazil.
[Metzger, Daniel] BC Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC, Canada.
[Cuny, Thomas; Klein, Marc] Univ Hosp, Dept Endocrinol, Nancy, France.
[Rabl, Wolfgang] Tech Univ Munich, Kinderklin, D-80290 Munich, Germany.
[Shah, Nalini] King Edward Mem Hosp, Dept Endocrinol, Bombay, Maharashtra, India.
[Jaffrain-Rea, Marie-Lise] Univ LAquila, Dept Biotechnol & Appl Clin Sci, LAquila & Neuromed Inst, IRCCS, Pozzilli, Italy.
[Zatelli, Maria Chiara] Univ Ferrara, Dept Med Sci, Sect Endocrinol, I-44100 Ferrara, Italy.
[Mantovani, Giovanna] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Endocrinol & Diabetol Unit, Dept Clin Sci & Community Hlth, Milan, Italy.
[Barlier, Anne] Aix Marseille Univ, Hop Concept, APHM, Lab Mol Biol, Marseilles, France.
[Barlier, Anne] CRNS, CRN2M UMR 7286, Marseille, France.
[Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
RP Beckers, A (reprint author), Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, Liege, Belgium.
EM albert.beckers@chu.ulg.ac.be
RI Trivellin, Giampaolo/J-6583-2016; Daly, Adrian /E-2178-2011;
Jaffrain-Rea, Marie-Lise/D-1129-2009;
OI Trivellin, Giampaolo/0000-0003-2384-4153; Daly, Adrian
/0000-0001-6130-2975; Jaffrain-Rea, Marie-Lise/0000-0002-5916-8997;
Cuny, Thomas/0000-0003-2944-5997
FU Fonds D'Investissement de Recherche Scientifique, CHU de Liege, Belgium;
US National Human Genome Research Institute/National Heart Lung and
Blood Institute [U54HG006542]; National Institute of Neurological
Disorders and Stroke [RO1 NS058529]
FX The work was supported in part by Fonds D'Investissement de Recherche
Scientifique, CHU de Liege, Belgium, and by the US National Human Genome
Research Institute/National Heart Lung and Blood Institute grant no.
U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and the
National Institute of Neurological Disorders and Stroke grant RO1
NS058529.
NR 49
TC 14
Z9 14
U1 3
U2 5
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD APR
PY 2016
VL 23
IS 4
BP 221
EP 233
DI 10.1530/ERC-16-0082
PG 13
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DO3OU
UT WOS:000377691700005
PM 26935837
ER
PT J
AU Kaewkhaw, R
Swaroop, M
Homma, K
Nakamura, J
Brooks, M
Kaya, KD
Chaitankar, V
Michael, S
Tawa, G
Zou, JZ
Rao, M
Zheng, W
Cogliati, T
Swaroop, A
AF Kaewkhaw, Rossukon
Swaroop, Manju
Homma, Kohei
Nakamura, Jutaro
Brooks, Matthew
Kaya, Koray Dogan
Chaitankar, Vijender
Michael, Sam
Tawa, Gregory
Zou, Jizhong
Rao, Mahendra
Zheng, Wei
Cogliati, Tiziana
Swaroop, Anand
TI Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina
Cultures Derived From Human Reporter Pluripotent Stem Cell Lines
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE human retina development; disease modeling; photoreceptor; high
throughput screening; chemical screens; drug discovery; transcriptome;
next generation sequencing; three-dimensional organoid culture;
fluorescent reporter
ID HUMAN IPS CELLS; GENE-THERAPY; PHOTORECEPTOR PRECURSORS; NEURAL RETINA;
REGENERATIVE MEDICINE; FATE DETERMINATION; VERTEBRATE RETINA; HUMAN
ESCS; DEGENERATION; EXPRESSION
AB We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration.
C1 [Kaewkhaw, Rossukon; Homma, Kohei; Nakamura, Jutaro; Brooks, Matthew; Kaya, Koray Dogan; Chaitankar, Vijender; Cogliati, Tiziana; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Kaewkhaw, Rossukon] Mahidol Univ, Ramathibodi Hosp, Fac Med, Res Ctr, Bangkok 10400, Thailand.
[Swaroop, Manju; Michael, Sam; Tawa, Gregory; Zheng, Wei] NIH, Natl Therapeut Rare & Neglected Dis, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Zou, Jizhong] NHLBI, iPSC Core, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA.
[Rao, Mahendra] New York Stem Cell Fdn, Res Inst, New York, NY USA.
[Homma, Kohei] Nippon Med Sch, Dept Physiol, 1-1-5 Sendagi, Tokyo 113, Japan.
[Nakamura, Jutaro] Yokohama City Univ, Dept Ophthalmol, Sch Med, Yokohama, Kanagawa 232, Japan.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Zheng, Wei/J-8889-2014;
OI Zheng, Wei/0000-0003-1034-0757; Swaroop, Anand/0000-0002-1975-1141
FU Intramural Research Program of the National Eye Institute, National
Institutes of Health [ZO1 EY000450, EY000474]; Japan Society for the
Promotion of Science (JSPS); JSPS Postdoctoral Fellowships for Research
Abroad (Kaitoku-NIH)
FX Supported by Intramural Research Program (ZO1 EY000450 and EY000474) of
the National Eye Institute, National Institutes of Health. KH and JN
were supported by grant-in-aid for Young Scientists (B) from the Japan
Society for the Promotion of Science (JSPS) and JSPS Postdoctoral
Fellowships for Research Abroad (Kaitoku-NIH).
NR 68
TC 0
Z9 0
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2016
VL 57
IS 5
SI SI
DI 10.1167/iovs.15-17639
PG 11
WC Ophthalmology
SC Ophthalmology
GA DO8NC
UT WOS:000378039300011
ER
PT J
AU Silson, EH
Groen, IIA
Kravitz, DJ
Baker, CI
AF Silson, Edward H.
Groen, Iris I. A.
Kravitz, Dwight J.
Baker, Chris I.
TI Evaluating the correspondence between face-, scene-, and
object-selectivity and retinotopic organization within lateral
occipitotemporal cortex
SO JOURNAL OF VISION
LA English
DT Article
DE retinotopy; category-selectivity; population receptive fields
ID HUMAN VISUAL-CORTEX; OCCIPITAL CORTEX; FIELD MAPS; EXTRASTRIATE CORTEX;
AREA; REPRESENTATIONS; PERCEPTION; BODY; RECOGNITION; ORIENTATION
AB The organization of human lateral occipitotemporal cortex (lOTC) has been characterized largely according to two distinct principles: retinotopy and category-selectivity. Whereas category-selective regions were originally thought to exist beyond retinotopic maps, recent evidence highlights overlap. Here, we combined detailed mapping of retinotopy, using population receptive fields (pRF), and category-selectivity to examine and contrast the retinotopic profiles of scene-(occipital place area, OPA), face- (occipital face area, OFA) and object- (lateral occipital cortex, LO) selective regions of lOTC. We observe striking differences in the relationship each region has to underlying retinotopy. Whereas OPA overlapped multiple retinotopic maps (including V3A, V3B, LO1, and LO2), and LO overlapped two maps (LO1 and LO2), OFA overlapped almost none. There appears no simple consistent relationship between category-selectivity and retinotopic maps, meaning category-selective regions are not constrained spatially to retinotopic map borders consistently. The multiple maps that overlap OPA suggests it is likely not appropriate to conceptualize it as a single scene-selective region, whereas the inconsistency in any systematic map overlapping OFA suggests it may constitute a more uniform area. Beyond their relationship to retinotopy, all three regions evidenced strongly retinotopic voxels, with pRFs exhibiting a significant bias towards the contralateral lower visual field, despite differences in pRF size, contributing to an emerging literature suggesting this bias is present across much of lOTC. Taken together, these results suggest that whereas category-selective regions are not constrained to consistently contain ordered retinotopic maps, they nonetheless likely inherit retinotopic characteristics of the maps from which they draw information.
C1 [Silson, Edward H.; Groen, Iris I. A.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Kravitz, Dwight J.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
RP Silson, EH (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM ed.silson@nih.gov
RI Groen, Iris/A-1462-2017
OI Groen, Iris/0000-0002-5536-6128
FU Intramural Research Program of the National Institute of Mental Health
[MH002909-08]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (MH002909-08).
NR 49
TC 1
Z9 1
U1 9
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 1534-7362
J9 J VISION
JI J. Vision
PD APR
PY 2016
VL 16
IS 6
AR 14
DI 10.1167/16.6.14
PG 21
WC Ophthalmology
SC Ophthalmology
GA DO7BX
UT WOS:000377938300014
PM 27105060
ER
PT J
AU Ladner, JT
Kuhn, JH
Palacios, G
AF Ladner, J. T.
Kuhn, J. H.
Palacios, G.
TI Standard finishing categories for high-throughput sequencing of viral
genomes
SO REVUE SCIENTIFIQUE ET TECHNIQUE-OFFICE INTERNATIONAL DES EPIZOOTIES
LA English
DT Article
DE Data curation; Genome assembly; High-throughput sequencing; Medical
countermeasure development; Molecular epidemiology; Population genomics;
Virus
ID EBOLA-VIRUS; DIVERSITY; EVOLUTION; DISCOVERY; VARIANTS; SURVEILLANCE;
CORONAVIRUS; POPULATION; EMERGENCE; EPIDEMIC
AB Viral genome sequencing has become the cornerstone of almost all aspects of virology. In particular, high-throughput, next-generation viral genome sequencing has become an integral part of molecular epidemiological investigations into outbreaks of viral disease, such as the recent outbreaks of Middle Eastern respiratory syndrome, Ebola virus disease and Zika virus infection. Multiple institutes have acquired the expertise and necessary infrastructure to perform such investigations, as evidenced by the accumulation of thousands of novel viral sequences over progressively shorter time periods. The authors recently proposed a nomenclature comprised of five high-throughput sequencing standard categories to describe the quality of determined viral genome sequences. These five categories (standard draft, high quality, coding complete, complete and finished) cover all levels of viral genome finishing and can be applied to sequences determined by any technology platform or assembly technique.
C1 [Ladner, J. T.; Palacios, G.] US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Frederick, MD 21702 USA.
[Kuhn, J. H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA.
RP Palacios, G (reprint author), US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Frederick, MD 21702 USA.
EM gustavo.f.palacios.ctr@mail.mil
RI Palacios, Gustavo/I-7773-2015
OI Palacios, Gustavo/0000-0001-5062-1938
FU Defense Threat Reduction Agency [1881290]; Battelle Memorial Institute's
prime contract; US National Institute of Allergy and Infectious Diseases
[HHSN272200700016I]
FX This work was partly funded by Defense Threat Reduction Agency Project
No. 1881290 and by Battelle Memorial Institute's prime contract with the
US National Institute of Allergy and Infectious Diseases under Contract
No. HHSN272200700016I. A subcontractor who performed this work is JHK,
an employee of Tunnell Government Services. The authors thank Laura
Bollinger for editing this manuscript.
NR 42
TC 1
Z9 1
U1 42
U2 46
PU OFFICE INT EPIZOOTIES
PI PARIS
PA 12 RUE DE PRONY, 75017 PARIS, FRANCE
SN 0253-1933
J9 REV SCI TECH OIE
JI Rev. Sci. Tech. Off. Int. Epizoot.
PD APR
PY 2016
VL 35
IS 1
BP 43
EP 52
DI 10.20506/rst.35.1.2416
PG 10
WC Veterinary Sciences
SC Veterinary Sciences
GA DO8EA
UT WOS:000378014200004
PM 27217167
ER
PT J
AU Hall, MD
Woolhouse, MEJ
Rambaut, A
AF Hall, M. D.
Woolhouse, M. E. J.
Rambaut, A.
TI Using genomics data to reconstruct transmission trees during disease
outbreaks
SO REVUE SCIENTIFIQUE ET TECHNIQUE-OFFICE INTERNATIONAL DES EPIZOOTIES
LA English
DT Article
DE Molecular epidemiology; Phylodynamics; Phylogenetics; Sequence analysis;
Transmission trees
ID MITOCHONDRIAL-DNA; VIRUS; DISTANCES
AB Genetic sequence data from pathogens present a novel means to investigate the spread of infectious disease between infected hosts or infected premises, complementing traditional contact-tracing approaches, and much recent work has gone into developing methods for this purpose. The objective is to recover the epidemic transmission tree, which identifies who infected whom. This paper reviews the various approaches that have been taken. The first step is to define a measure of difference between sequences, which must be done while taking into account such factors as recombination and convergent evolution. Three broad categories of method exist, of increasing complexity: those that assume no within host genetic diversity or mutation, those that assume no within-host diversity but allow mutation, and those that allow both. Until recently, the assumption was usually made that every host in the epidemic could be identified, but this is now being relaxed, and some methods are intended for sparsely sampled data, concentrating on the identification of pairs of sequences that are likely to be the result of direct transmission rather than inferring the complete transmission tree. Many of the procedures described here are available to researchers as free software.
C1 [Hall, M. D.; Woolhouse, M. E. J.; Rambaut, A.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Hall, M. D.; Woolhouse, M. E. J.; Rambaut, A.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Hall, M. D.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London SW7 2AZ, England.
[Rambaut, A.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Hall, MD (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.; Hall, MD (reprint author), Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.; Hall, MD (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London SW7 2AZ, England.
EM matthew.hall@imperial.ac.uk
FU Scottish Government; European Research Council (ERC) under the European
Community [278433-PREDEMICS]; ERC [260864]; European Union [643476]
FX MDH was supported by a PhD studentship from the Scottish
Government-funded EPIC program. AR has received funding from the
European Research Council (ERC) under the European Community's Seventh
Framework Programme (FP7/2007-2013) under Grant Agreement No.
278433-PREDEMICS and ERC Grant Agreement No. 260864. MEJW acknowledges
support from a European Union Horizon 2020 grant (COMPARE, #643476).
NR 28
TC 0
Z9 0
U1 7
U2 7
PU OFFICE INT EPIZOOTIES
PI PARIS
PA 12 RUE DE PRONY, 75017 PARIS, FRANCE
SN 0253-1933
J9 REV SCI TECH OIE
JI Rev. Sci. Tech. Off. Int. Epizoot.
PD APR
PY 2016
VL 35
IS 1
BP 287
EP 296
DI 10.20506/rst.35.1.2433
PG 10
WC Veterinary Sciences
SC Veterinary Sciences
GA DO8EA
UT WOS:000378014200021
PM 27217184
ER
PT J
AU McClelland, KS
Bowles, J
AF McClelland, Kathryn S.
Bowles, Josephine
TI Culturing murine embryonic organs: Pros, cons, tips and tricks
SO DIFFERENTIATION
LA English
DT Article
DE Organ culture; Ex vivo; Filter culture; Agar block culture; Hanging
drop; Culture conditions
ID GERM-CELL FATE; XY GONAD; MOUSE; MICE; PANCREAS; MORPHOGENESIS;
MIGRATION; MEIOSIS; SYSTEM; KIDNEY
AB There are three established techniques described for ex vivo culture of the early embryonic organs: filter culture, agar block culture and hanging drop culture. Each of these protocols has advantages and disadvantages; here we assess the merits of each approach. Agar block culture has a long history and has been well described. This method results in good embryonic organ morphology. Filter culture has been used to culture a number of different embryonic organs and there are a variety of filter choices available. The key disadvantage of agar-block and filter based culture is that the large amount of media required can make the approach expensive, especially if biologicals such as growth factors are necessary; in addition, using these methods it can be difficult to track particular samples. Hanging drop culture is most commonly used to enable the aggregation of embryonic stem cells into embryoid bodies but it has also been employed for ex vivo organ culture. This method requires only 40 mu L of media per drop and isolates every organ to a trackable unit. We describe each of these methods and the use of different medias and provide the user with a matrix to help determine the optimal culture method for their needs. Glass based culture methods required for live imaging are not discussed here. Crown Copyright (C) 2016 Published by Elsevier B.V. on behalf of International Society of Differentiation All rights reserved.
C1 [McClelland, Kathryn S.; Bowles, Josephine] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
[McClelland, Kathryn S.] NIEHS, Dev Reprod Biol Grp, Reprod Dev Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Bowles, J (reprint author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
EM j.bowles@imb.uq.edu.au
RI Bowles, Josephine/B-6583-2013;
OI Bowles, Josephine/0000-0003-2867-7438; McClelland, Kathryn
S/0000-0003-2845-5448
FU Australian Research Council (ARC) [DP140104059]; National Health and
Medical Research Council of Australia (NHMRC) [APP1074258]
FX We thank Peter Koopman for supervising the work that refined these
protocols. We thank Alex Combes, Lee Niswander and Lori Sussel for
helpful discussions and sharing personal and lab culture experience. We
thank Humphrey Yao for helpful comments on this manuscript and Barbara
Nicol for her assistance. This work was supported by research Grants
from the Australian Research Council (grant number DP140104059) (ARC)
and National Health and Medical Research Council of Australia (grant
number APP1074258) (NHMRC). Confocal microscopy was performed at the
Australian Cancer Research Foundation Dynamic Imaging Centre for Cancer
Biology.
NR 30
TC 1
Z9 1
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
EI 1432-0436
J9 DIFFERENTIATION
JI Differentiation
PD APR-JUN
PY 2016
VL 91
IS 4-5
BP 50
EP 56
DI 10.1016/j.diff.2016.01.008
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DO2OQ
UT WOS:000377619800008
PM 26988290
ER
PT J
AU McClelland, KS
Ng, ET
Bowles, J
AF McClelland, Kathryn S.
Ee Ting Ng
Bowles, Josephine
TI Agarose/gelatin immobilisation of tissues or embryo segments for
orientated paraffin embedding and sectioning
SO DIFFERENTIATION
LA English
DT Review
DE Embedding; Sectioning; Orientated sample; Agarose; Immobilisation
AB The technique described in this protocol allows the user to position small tissues in the optimal orientation for paraffin embedding and sectioning by first immobilising the tissue in an agarose/gelatin cube. This method is an adaptation of methods used for early embryos and can be used for any small tissues or embryo segments. Processing of larger tissue sections using molds to create agarose/gelatin blocks has been described previously; this detailed protocol provides a method for dealing with much smaller tissues or embryos (<= 5 mm). The tissue is briefly fixed then an agarose/gelatin drop is created to surround the tissue. The tissue can be orientated as per the user's preference in the drop before it sets as is carved into a cube with a domed top. The cube is then dehydrated and goes through the embedding and sectioning process. The domed cube is easy to orientate when embedding the tissue in a wax block giving the user assured orientation of the small tissue for sectioning. Additionally, the agarose/gelatin cube is easy to see in the unmolded wax once embedded, making the region of interest easy to identify. Crown Copyright (C) 2016 Published by Elsevier B.V. on behalf of International Society of Differentiation All rights reserved.
C1 [McClelland, Kathryn S.; Ee Ting Ng; Bowles, Josephine] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
[McClelland, Kathryn S.] Natl Inst Environm Hlth Sci, Reprod Dev Biol Lab, Dev Reprod Biol Grp, Res Triangle Pk, NC USA.
RP Bowles, J (reprint author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
EM j.bowles@imb.uq.edu.au
RI Bowles, Josephine/B-6583-2013;
OI Bowles, Josephine/0000-0003-2867-7438; McClelland, Kathryn
S/0000-0003-2845-5448
FU Australian Research Council (ARC); National Health and Medical Research
Council of Australia (NHMRC)
FX We thank Terje Svingen and Peter Koopman for supervising the work that
refined this protocol. We thank Ivy Chiang for helpful discussions. This
work was supported by research grants from the Australian Research
Council (ARC) and the National Health and Medical Research Council of
Australia (NHMRC). Confocal microscopy was performed at the Australian
Cancer Research Foundation Dynamic Imaging Centre for Cancer Biology.
NR 5
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
EI 1432-0436
J9 DIFFERENTIATION
JI Differentiation
PD APR-JUN
PY 2016
VL 91
IS 4-5
BP 68
EP 71
DI 10.1016/j.diff.2015.12.001
PG 4
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DO2OQ
UT WOS:000377619800010
PM 26742717
ER
PT J
AU Tanigawa, S
Perantoni, AO
AF Tanigawa, Shunsuke
Perantoni, Alan O.
TI Modeling renal progenitors - defining the niche
SO DIFFERENTIATION
LA English
DT Review
ID EMBRYONIC STEM-CELLS; METANEPHRIC MESENCHYME; KIDNEY DEVELOPMENT;
SELF-RENEWAL; URETERAL BUD; NEPHRON PROGENITORS; MAMMALIAN KIDNEY; MOUSE
KIDNEY; EPITHELIAL TRANSFORMATION; INTERMEDIATE MESODERM
AB Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+ progenitor. Published by Elsevier B.V. on behalf of International Society of Differentiation
C1 [Tanigawa, Shunsuke] Kumamoto Univ, Inst Mol Embryol & Genet, Dept Kidney Dev, 2-2-1 Honjo, Kumamoto 8600811, Japan.
[Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
RP Perantoni, AO (reprint author), NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
EM perantoa@mail.nih.gov
FU Japanese Society for the Promotion of Science; grant KAKENHI from the
Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan [KAKENHI 26860640]; Intramural Research Program of the NIH, NCI,
CCR
FX This work was supported by a fellowship from the Japanese Society for
the Promotion of Science (to S.T.), grant KAKENHI 26860640 from the
Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan (to S.T.), and the Intramural Research Program of the NIH, NCI,
CCR.
NR 57
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
EI 1432-0436
J9 DIFFERENTIATION
JI Differentiation
PD APR-JUN
PY 2016
VL 91
IS 4-5
BP 152
EP 158
DI 10.1016/j.diff.2016.01.007
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DO2OQ
UT WOS:000377619800019
PM 26856661
ER
PT J
AU Campbell, LA
Ritchie, C
Heathward, E
Harvey, BK
AF Campbell, L. A.
Ritchie, C.
Heathward, E.
Harvey, B. K.
TI USING CRISPR/CAS9 TO CREATE HIV-NANOLUC CHME-5, A NOVEL MICROGLIA CELL
LINE.
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Campbell, L. A.; Ritchie, C.; Heathward, E.; Harvey, B. K.] NIDA, Optogenet & Transgen Technol Core, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
EI 1557-1904
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2016
VL 11
SU 1
BP S8
EP S8
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DO1UY
UT WOS:000377566000016
ER
PT J
AU Harry, GJ
AF Harry, G. J.
TI NEUROINFLAMMATION: DISSECTING MICROGLIA PHENOTYPES AND CONTRIBUTIONS TO
INJURY AND REPAIR
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Harry, G. J.] NIEHS, Neurotoxicol Grp, Natl Toxicol Program Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
EI 1557-1904
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2016
VL 11
SU 1
BP S53
EP S53
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DO1UY
UT WOS:000377566000136
ER
PT J
AU Mocchetti, I
Tessarollo, L
Bachis, A
AF Mocchetti, Italo
Tessarollo, L.
Bachis, A.
TI PROBDNF, P75NTR AND HIV-MEDIATED NEUROTOXICITY
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Mocchetti, Italo; Bachis, A.] Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA.
[Tessarollo, L.] NCI, MCGP, Ft Detrick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
EI 1557-1904
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2016
VL 11
SU 1
BP S54
EP S54
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DO1UY
UT WOS:000377566000138
ER
PT J
AU Rom, S
Zuluaga-Ramirez, V
Reichenbach, NL
Dykstra, H
Gajghate, S
Pacher, P
Persidsky, Y
AF Rom, S.
Zuluaga-Ramirez, V
Reichenbach, N. L.
Dykstra, H.
Gajghate, S.
Pacher, P.
Persidsky, Y.
TI EFFECTS ON INTEGRINS/CYTOSKELETON BY PARP INHIBITION IN LEUKOCYTES
DIMINISH INFLAMMATION AND PROTECTS THE BLOOD BRAIN BARRIER.
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Rom, S.; Zuluaga-Ramirez, V; Reichenbach, N. L.; Dykstra, H.; Gajghate, S.; Persidsky, Y.] Temple Univ, Lewis Katz Sch Med, Dept Pathol, Philadelphia, PA 19140 USA.
[Pacher, P.] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
EI 1557-1904
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2016
VL 11
SU 1
BP S42
EP S42
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DO1UY
UT WOS:000377566000107
ER
PT J
AU Goldstein, DS
Sims-O'Neil, C
AF Goldstein, David S.
Sims-O'Neil, Cathy
TI Systemic hemodynamics during orthostasis in multiple system atrophy
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Letter
DE Multiple system atrophy; Total peripheral resistance; Stroke volume;
Orthostatic hypotension; Autonomic failure
C1 [Goldstein, David S.; Sims-O'Neil, Cathy] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, NIH, 9000 Rockville Pike,10-5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
OI Goldstein, David/0000-0002-5709-9940
FU Intramural NIH HHS [ZIA NS003034-10, ZIA NS003033-10, Z01 NS003033-01];
PHS HHS [1ZIANS003034]
NR 3
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD APR
PY 2016
VL 25
BP 106
EP 107
DI 10.1016/j.parkreldis.2016.02.009
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DK0QD
UT WOS:000374616400019
PM 26920338
ER
PT J
AU Sun, R
Urban, JF
Notari, L
Vanuytsel, T
Madden, KB
Bohl, JA
Ramalingam, TR
Wynn, TA
Zhao, AP
Shea-Donohue, T
AF Sun, Rex
Urban, Joseph F., Jr.
Notari, Luigi
Vanuytsel, Tim
Madden, Kathleen B.
Bohl, Jennifer A.
Ramalingam, Thirumalai R.
Wynn, Thomas A.
Zhao, Aiping
Shea-Donohue, Terez
TI Interleukin-13 Receptor alpha 1-Dependent Responses in the Intestine Are
Critical to Parasite Clearance
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ALTERNATIVELY ACTIVATED MACROPHAGES; EPITHELIAL-CELL FUNCTION;
NIPPOSTRONGYLUS-BRASILIENSIS INFECTION; HELIGMOSOMOIDES-POLYGYRUS;
PROTECTIVE IMMUNITY; NEMATODE INFECTIONS; ENTERIC NEMATODES; TH2
CYTOKINE; MURINE GUT; T-CELLS
AB Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13R alpha 1 and IL-4R alpha chains. We used mice deficient in IL-13R alpha 1 (IL-13R alpha 1(-/-)) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri. There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13R alpha 2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13R alpha 1(-/-) mice. Goblet cell numbers and resistin-like molecule beta (RELM-beta) expression were attenuated significantly in IL-13R alpha 1(-/-) mice following Hb2 infections. IL-13R alpha 1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13R alpha 1(-/-) mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13R alpha 1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.
C1 [Sun, Rex; Notari, Luigi; Bohl, Jennifer A.; Zhao, Aiping; Shea-Donohue, Terez] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA.
[Sun, Rex; Notari, Luigi; Bohl, Jennifer A.; Zhao, Aiping; Shea-Donohue, Terez] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Vanuytsel, Tim] Univ Leuven, Translat Res Ctr Gastrointestinal Disorders TARGI, Leuven, Belgium.
[Madden, Kathleen B.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
[Ramalingam, Thirumalai R.; Wynn, Thomas A.] NIAID, Div Parasitol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD USA.
RP Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA.; Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
EM tdonohue@mbrc.umaryland.edu
FU NIH [R01-AI/DK49316, R01-DK083418]; USDA [1235-51000-055]
FX NIH provided funding to Terez Shea-Donohue under grant number
R01-AI/DK49316. NIH provided funding to Aiping Zhao under grant number
R01-DK083418. USDA provided funding to Joseph F. Urban under grant
number CRIS project #1235-51000-055.
NR 41
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2016
VL 84
IS 4
BP 1032
EP 1044
DI 10.1128/IAI.00990-15
PG 13
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DN5JV
UT WOS:000377103600015
PM 26810038
ER
PT J
AU De Pascalis, R
Mittereder, L
Kennett, NJ
Elkins, KL
AF De Pascalis, Roberto
Mittereder, Lara
Kennett, Nikki J.
Elkins, Karen L.
TI Activities of Murine Peripheral Blood Lymphocytes Provide Immune
Correlates That Predict Francisella tularensis Vaccine Efficacy
SO INFECTION AND IMMUNITY
LA English
DT Article
ID T-CELL RESPONSES; MYCOBACTERIAL GROWTH; PROTECTIVE IMMUNITY; LVS
INFECTION; B-CELLS; STRAIN; TULAREMIA; TUBERCULOSIS; ANTIBODIES;
SUBPOPULATIONS
AB We previously identified potential correlates of vaccine-induced protection against Francisella tularensis using murine splenocytes and further demonstrated that the relative levels of gene expression varied significantly between tissues. In contrast to splenocytes, peripheral blood leukocytes (PBLs) represent a means to bridge vaccine efficacy in animal models to that in humans. Here we take advantage of this easily accessible source of immune cells to investigate cell-mediated immune responses against tularemia, whose sporadic incidence makes clinical trials of vaccines difficult. Using PBLs from mice vaccinated with F. tularensis Live Vaccine Strain (LVS) and related attenuated strains, we combined the control of in vitro Francisella replication within macrophages with gene expression analyses. The in vitro functions of PBLs, particularly the control of intramacrophage LVS replication, reflected the hierarchy of in vivo protection conferred by LVS-derived vaccines. Moreover, several genes previously identified by the evaluation of splenocytes were also found to be differentially expressed in immune PBLs. In addition, more extensive screening identified additional potential correlates of protection. Finally, expression of selected genes in mouse PBLs obtained shortly after vaccination, without ex vivo restimulation, was different among vaccine groups, suggesting a potential tool to monitor efficacious vaccine-induced immune responses against F. tularensis. Our studies demonstrate that murine PBLs can be used productively to identify potential correlates of protection against F. tularensis and to expand and refine a comprehensive set of protective correlates.
C1 [De Pascalis, Roberto; Mittereder, Lara; Kennett, Nikki J.; Elkins, Karen L.] US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Mittereder, Lara] NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP De Pascalis, R (reprint author), US FDA, Lab Mucosal Pathogens & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
EM roberto.depascalis@fda.hhs.gov
NR 38
TC 2
Z9 2
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2016
VL 84
IS 4
BP 1054
EP 1061
DI 10.1128/IAI.01348-15
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DN5JV
UT WOS:000377103600017
PM 26810039
ER
PT J
AU Roffe, E
Marino, APMP
Weaver, J
Wan, WZ
de Araujo, FF
Hoffman, V
Santiago, HC
Murphy, PM
AF Roffe, Ester
Marino, Ana Paula M. P.
Weaver, Joseph
Wan, Wuzhou
de Araujo, Fernanda F.
Hoffman, Victoria
Santiago, Helton C.
Murphy, Philip M.
TI Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis
Driven by Pathogen-Specific Type I Immunity in Mice
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CHRONIC CHAGAS-DISEASE; CD8(+) T-CELLS; POLYARTERITIS-NODOSA; AMERICAN
TRYPANOSOMIASIS; PARASITE PERSISTENCE; SKELETAL-MUSCLE; MYOCARDITIS;
INFECTION; INVOLVEMENT; NOMENCLATURE
AB Infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain of Trypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80(+) macrophages, and T. cruzi tetramer-specific CD8(+) T lymphocytes capable of producing gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) but not interleukin-17 (IL-17). T. cruzi-specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus, T. cruzi infection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses.
C1 [Roffe, Ester; Marino, Ana Paula M. P.; Weaver, Joseph; Wan, Wuzhou; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[de Araujo, Fernanda F.] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Lab Emerging Pathogens, Silver Spring, MD USA.
[Hoffman, Victoria] NIH, Div Vet Resources, Off Res Serv, Off Director, Bethesda, MD USA.
[Santiago, Helton C.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Roffe, Ester] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Imunol Celular & Mol, Belo Horizonte, MG, Brazil.
[Marino, Ana Paula M. P.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Imunopatol, Belo Horizonte, MG, Brazil.
[de Araujo, Fernanda F.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Biomarcadores Diagnost & Monitoracao, Belo Horizonte, MG, Brazil.
[Santiago, Helton C.] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil.
RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pmm@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, NIH
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH.
NR 40
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2016
VL 84
IS 4
BP 1123
EP 1136
DI 10.1128/IAI.01497-15
PG 14
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DN5JV
UT WOS:000377103600024
PM 26857570
ER
PT J
AU Binkley, N
Dawson-Hughes, B
Durazo-Arvizu, R
Thamm, M
Merkel, J
Sempos, C
AF Binkley, N.
Dawson-Hughes, B.
Durazo-Arvizu, R.
Thamm, M.
Merkel, J.
Sempos, C.
TI VITAMIN D MEASUREMENT STANDARDIZATION: THE WAY OUT OF THE CHAOS
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and
Musculoskeletal Diseases
CY APR 14-17, 2016
CL Malaga, SPAIN
SP WCO, IOF, ESCEO
C1 [Binkley, N.] Univ Wisconsin, Osteoporosis Clin Res Program, Madison, WI 53706 USA.
[Binkley, N.] Univ Wisconsin, Inst Aging, Madison, WI 53706 USA.
[Dawson-Hughes, B.] Tufts Univ, USDA Nutr Res Ctr, Boston, MA 02111 USA.
[Durazo-Arvizu, R.] Loyola Univ Chicago, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL USA.
[Thamm, M.] Robert Koch Inst, Berlin, Germany.
[Merkel, J.; Sempos, C.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD APR
PY 2016
VL 27
SU 1
MA OC18
BP S49
EP S49
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DM6NH
UT WOS:000376469100029
ER
PT J
AU Schaap, LA
Simonsick, EM
Newman, AB
Schwartz, AV
Caserotti, P
Kritchevsky, SB
Goodpaster, BH
Harris, TB
Visser, M
AF Schaap, L. A.
Simonsick, E. M.
Newman, A. B.
Schwartz, A. V.
Caserotti, P.
Kritchevsky, S. B.
Goodpaster, B. H.
Harris, T. B.
Visser, M.
TI SARCOPENIA DEFINITION PARAMETERS AND INCIDENT DISABILITY
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and
Musculoskeletal Diseases
CY APR 14-17, 2016
CL Malaga, SPAIN
SP WCO, IOF, ESCEO
C1 [Schaap, L. A.; Visser, M.] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Hlth Sci, Amsterdam, Netherlands.
[Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Schwartz, A. V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Caserotti, P.] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Kritchevsky, S. B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Goodpaster, B. H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD APR
PY 2016
VL 27
SU 1
MA OC25
BP S53
EP S53
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DM6NH
UT WOS:000376469100036
ER
PT J
AU Scott, JR
Courter, JD
Saldana, SN
Widemann, BC
Fisher, M
Weiss, B
Perentesis, J
Vinks, AA
AF Scott, Jeffrey R.
Courter, Joshua D.
Saldana, Shannon N.
Widemann, Brigitte C.
Fisher, Michael
Weiss, Brian
Perentesis, John
Vinks, Alexander A.
CA Neurofibromatosis Clinical Trials
TI Population pharmacokinetics of sirolimus in pediatric patients with
neurofibromatosis type 1 (vol 35, pg 332, 2013)
SO THERAPEUTIC DRUG MONITORING
LA English
DT Correction
C1 [Scott, Jeffrey R.; Courter, Joshua D.; Saldana, Shannon N.] Cincinnati Childrens Hosp Med Ctr, Div Pharma, Cincinnati, OH 45229 USA.
[Saldana, Shannon N.; Vinks, Alexander A.] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, 3333 Burnet Ave,MLC 6018, Cincinnati, OH 45229 USA.
[Saldana, Shannon N.; Weiss, Brian; Perentesis, John; Vinks, Alexander A.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA.
[Weiss, Brian; Perentesis, John] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fisher, Michael] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Scott, Jeffrey R.] St Jude Childrens Res Hosp, Dept Pharm, Memphis, TN 38105 USA.
RP Vinks, AA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, 3333 Burnet Ave,MLC 6018, Cincinnati, OH 45229 USA.
EM Sander.vinks@cchmc.org
NR 1
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0163-4356
EI 1536-3694
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD APR
PY 2016
VL 38
IS 2
BP 284
EP 284
PG 1
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA DN3BT
UT WOS:000376938000014
ER
PT J
AU Lockhart, SR
Fothergill, AW
Iqbal, N
Bolden, CB
Grossman, NT
Garvey, EP
Brand, SR
Hoekstra, WJ
Schotzinger, RJ
Ottinger, E
Patterson, TF
Wiederhold, NP
AF Lockhart, Shawn R.
Fothergill, Annette W.
Iqbal, Naureen
Bolden, Carol B.
Grossman, Nina T.
Garvey, Edward P.
Brand, Stephen R.
Hoekstra, William J.
Schotzinger, Robert J.
Ottinger, Elizabeth
Patterson, Thomas F.
Wiederhold, Nathan P.
TI The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent
In Vitro Activity against Cryptococcus neoformans and Cryptococcus
gattii
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ANTIFUNGAL SUSCEPTIBILITIES
AB The in vitro activities of the novel fungal Cyp51 inhibitor VT-1129 were evaluated against a large panel of Cryptococcus neoformans and Cryptococcus gattii isolates. VT-1129 demonstrated potent activities against both Cryptococcus species as demonstrated by low MIC50 and MIC90 values. For C. gattii, the in vitro potency was maintained against all genotypes. In addition, significantly lower geometric mean MICs were observed for VT-1129 than for fluconazole against C. neoformans, including isolates with reduced fluconazole susceptibility.
C1 [Lockhart, Shawn R.; Iqbal, Naureen; Bolden, Carol B.; Grossman, Nina T.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA.
[Fothergill, Annette W.; Patterson, Thomas F.; Wiederhold, Nathan P.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA.
[Garvey, Edward P.; Brand, Stephen R.; Hoekstra, William J.; Schotzinger, Robert J.] Viamet Pharmaceut Inc, Durham, NC USA.
[Ottinger, Elizabeth] NIH, Therapeut Rare & Neglected Dis Bethesda, Bldg 10, Bethesda, MD 20892 USA.
[Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Wiederhold, NP (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA.
EM wiederholdn@uthscsa.edu
FU National Institutes of Health National Institute of Allergy and
Infectious Diseases [N01-AI-25475]; National Institutes of Health,
National Center for Advancing Translational Sciences, Therapeutics for
Rare and Neglected Diseases (TRND) Program; Viamet Pharmaceuticals, Inc.
FX This project was funded by the National Institutes of Health National
Institute of Allergy and Infectious Diseases under contract no.
N01-AI-25475 (Thomas F. Patterson), the National Institutes of Health,
National Center for Advancing Translational Sciences, Therapeutics for
Rare and Neglected Diseases (TRND) Program (Shawn R. Lockhart), and
Viamet Pharmaceuticals, Inc. (Nathan P. Wiederhold). VT-1129 powder was
provided by Viamet Pharmaceuticals, Inc.
NR 18
TC 2
Z9 2
U1 2
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD APR
PY 2016
VL 60
IS 4
BP 2528
EP 2531
DI 10.1128/AAC.02770-15
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA DM6XL
UT WOS:000376496100072
PM 26787697
ER
PT J
AU Tadesse, DA
Singh, A
Zhao, SH
Bartholomew, M
Womack, N
Ayers, S
Fields, PI
McDermott, PF
AF Tadesse, Daniel A.
Singh, Aparna
Zhao, Shaohua
Bartholomew, Mary
Womack, Niketta
Ayers, Sherry
Fields, Patricia I.
McDermott, Patrick F.
TI Antimicrobial Resistance in Salmonella in the United States from 1948 to
1995
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ESCHERICHIA-COLI; DRUG-RESISTANCE; FOOD ANIMALS; INFECTIONS;
TYPHIMURIUM; STRAINS; HUMANS; EMERGENCE; INCREASE
AB We conducted a retrospective study of 2,149 clinical Salmonella strains to help document the historical emergence of antimicrobial resistance. There were significant increases in resistance to older drugs, including ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline, which were most common in Salmonella enterica serotype Typhimurium. An increase in multidrug resistance was observed for each decade since the 1950s. These data help show how Salmonella evolved over the past 6 decades, after the introduction of new antimicrobial agents.
C1 [Tadesse, Daniel A.; Zhao, Shaohua; Womack, Niketta; Ayers, Sherry; McDermott, Patrick F.] US FDA, Ctr Vet Med, US Dept Hlth & Human Serv, Laurel, MD USA.
[Singh, Aparna] NIH, US Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA.
[Bartholomew, Mary] US FDA, Ctr Vet Med, US Dept Hlth & Human Serv, Rockville, MD 20857 USA.
[Fields, Patricia I.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, US Dept Hlth & Human Serv, Atlanta, GA USA.
RP McDermott, PF (reprint author), Ctr Dis Control & Prevent, Ctr Surveillance Epidemiol & Lab Serv, US Dept Hlth & Human Serv, Atlanta, GA USA.
EM patrick.mcdermott@fda.hhs.gov
FU U.S. Food and Drug Administration, Center for Veterinary Medicine,
Office of Research [223-02-7010]
FX The study isolates were collected by American Type Culture Collection
(ATCC) through a contract agreement with the U.S. Food and Drug
Administration, Center for Veterinary Medicine, Office of Research
(contract 223-02-7010).
NR 28
TC 1
Z9 1
U1 2
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD APR
PY 2016
VL 60
IS 4
BP 2567
EP 2571
DI 10.1128/AAC.02536-15
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA DM6XL
UT WOS:000376496100082
PM 26856840
ER
PT J
AU Espinoza, JA
Bizama, C
Garcia, P
Ferreccio, C
Javle, M
Miguel, JF
Koshiol, J
Roa, JC
AF Espinoza, Jaime A.
Bizama, Carolina
Garcia, Patricia
Ferreccio, Catterina
Javle, Milind
Miguel, Juan F.
Koshiol, Jill
Roa, Juan C.
TI The inflammatory inception of gallbladder cancer
SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
LA English
DT Review
DE Gallbladder cancer; Gallstones; Chronic inflammation; Metaplasia;
Salmonella Typhi; TP53
ID PRIMARY SCLEROSING CHOLANGITIS; BILIARY-TRACT CANCERS; CHOLESTEROL
GALLSTONE FORMATION; LIVER X RECEPTORS; PANCREATICOBILIARY MALJUNCTION;
INTESTINAL METAPLASIA; PRENEOPLASTIC LESIONS; GENE POLYMORPHISMS;
SALMONELLA-TYPHI; BILE-DUCT
AB Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasiadysplasia-carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted. (C) 2016 Published by Elsevier B.V.
C1 [Espinoza, Jaime A.] Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, SciLifeLab, SE-17176 Stockholm, Sweden.
[Bizama, Carolina; Garcia, Patricia; Roa, Juan C.] Pontificia Univ Catolica Chile, Sch Med, UC Ctr Invest Oncol CITO, Dept Pathol,Adv Ctr Chron Dis ACCDiS, Santiago 8330024, Chile.
[Ferreccio, Catterina] Pontificia Univ Catolica Chile, Sch Med, Adv Ctr Chron Dis ACCDiS, Dept Publ Hlth, Santiago 8330024, Chile.
[Javle, Milind] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Miguel, Juan F.] Pontificia Univ Catolica Chile, Sch Med, Dept Gastroenterol, Santiago 8330024, Chile.
[Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20850 USA.
RP Roa, JC (reprint author), Pontificia Univ Catolica Chile, Marcoleta 377,7th Floor, Santiago, Chile.
EM jcroa@med.puc.cl
OI Espinoza, Jaime/0000-0002-0731-2715
FU FONDECYT Fondo Nacional de Investigation y Tecnologia [JAE-3140308,
CA-3140426, PG-11130515, JFM-1130303, JCR-1130204]; FONDAP Fondo de
Financiamiento de Centros de Investigation en Areas Prioritarias ACCDiS
[JCR-15130011]; Intramural Research Program of the National Institutes
of Health and National Cancer Institute, Division of Cancer Epidemiology
and Genetics (DCEG)
FX This review was supported by FONDECYT Fondo Nacional de Investigation y
Tecnologia (JAE-3140308, CA-3140426, PG-11130515, JFM-1130303, and
JCR-1130204), FONDAP Fondo de Financiamiento de Centros de Investigation
en Areas Prioritarias ACCDiS (JCR-15130011), and general funds from the
Intramural Research Program of the National Institutes of Health and
National Cancer Institute, Division of Cancer Epidemiology and Genetics
(DCEG). We thank Maria Jose Apud for her expert work in figure design.
NR 152
TC 2
Z9 2
U1 5
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-419X
EI 0006-3002
J9 BBA-REV CANCER
JI Biochim. Biophys. Acta-Rev. Cancer
PD APR
PY 2016
VL 1865
IS 2
BP 245
EP 254
DI 10.1016/j.bbcan.2016.03.004
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Oncology
SC Biochemistry & Molecular Biology; Biophysics; Oncology
GA DM7NB
UT WOS:000376546200016
PM 26980625
ER
PT J
AU Cumming, BG
Nienborg, H
AF Cumming, Bruce G.
Nienborg, Hendrikje
TI Feedforward and feedback sources of choice probability in neural
population responses
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID DECISION-RELATED ACTIVITY; PRIMARY VISUAL-CORTEX; SENSORY NEURONS; AREA
MT; CORTICAL AREA; INTERNEURONAL CORRELATIONS; DISPARITY DISCRIMINATION;
CORRELATED VARIABILITY; BEHAVIORAL PERFORMANCE; BAYESIAN-INFERENCE
AB How the processing of signals carried by sensory neurons supports perceptual decisions is a long-standing question in neuroscience. The ability to record neuronal activity in awake animals while they perform psychophysical tasks near threshold has been a key advance in studying these questions. Trial-to-trial correlations between the activity of sensory neurons and the decisions reported by animals ('hoice probabilities'), even when measured across repeated presentations of an identical stimulus provide insights into this problem. But understanding the sources of such co-variability between sensory neurons and behavior has proven more difficult than it initially appeared. Below, we discuss our current understanding of what gives rise to these correlations.
C1 [Cumming, Bruce G.] NEI, NIH, Bethesda, MD 20892 USA.
[Nienborg, Hendrikje] Univ Tubingen, Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
RP Cumming, BG (reprint author), NEI, NIH, Bethesda, MD 20892 USA.; Nienborg, H (reprint author), Univ Tubingen, Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
EM bgc@lsr.nei.nih.gov; hendrikje.nienborg@cin.uni-tuebingen.de
FU National Institutes of Health-National Eye Institute; European Research
Council (NEUROOPTOGEN)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health-National Eye Institute and a Starting
Independent Researcher grant to H.N. from the European Research Council
(project acronym: NEUROOPTOGEN).
NR 70
TC 3
Z9 3
U1 2
U2 4
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
EI 1873-6882
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD APR
PY 2016
VL 37
BP 126
EP 132
DI 10.1016/j.conb.2016.01.009
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DM7NC
UT WOS:000376546300019
PM 26922005
ER
PT J
AU Leoncini, E
Edefonti, V
Hashibe, M
Parpinel, M
Cadoni, G
Ferraroni, M
Serraino, D
Matsuo, K
Olshan, AF
Zevallos, JP
Winn, DM
Moysich, K
Zhang, ZF
Morgenstern, H
Levi, F
Kelsey, K
McClean, M
Bosetti, C
Schantz, S
Yu, GP
Boffetta, P
Lee, YCA
Chuang, SC
Decarli, A
La Vecchia, C
Boccia, S
AF Leoncini, Emanuele
Edefonti, Valeria
Hashibe, Mia
Parpinel, Maria
Cadoni, Gabriella
Ferraroni, Monica
Serraino, Diego
Matsuo, Keitaro
Olshan, Andrew F.
Zevallos, Jose P.
Winn, Deborah M.
Moysich, Kirsten
Zhang, Zuo-Feng
Morgenstern, Hal
Levi, Fabio
Kelsey, Karl
McClean, Michael
Bosetti, Cristina
Schantz, Stimson
Yu, Guo-Pei
Boffetta, Paolo
Lee, Yuan-Chin Amy
Chuang, Shu-Chun
Decarli, Adriano
La Vecchia, Carlo
Boccia, Stefania
TI Carotenoid intake and head and neck cancer: a pooled analysis in the
International Head and Neck Cancer Epidemiology Consortium
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Carotenoids; Head and neck cancer; Nutrients; Diet
ID UPPER AERODIGESTIVE TRACT; PHARYNGEAL CANCER; BETA-CAROTENE;
LARYNGEAL-CANCER; PROSPECTIVE COHORT; LUNG-CANCER; ORAL-CANCER;
VITAMIN-A; RISK; DIET
AB Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39 % (95 % CI 29-47 %) for oral/pharyngeal cancer and 39 % (95 % CI 24-50 %) for laryngeal cancer. Intakes of beta-carotene equivalents, beta-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18 % reduction in the rate of oral and pharyngeal cancer (95 % CI 6-29 %) and 17 % reduction in the rate of laryngeal cancer (95 % CI 0-32 %). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p < 0.05). The odds ratio for the combined effect of low carotenoid intake and high alcohol or tobacco consumption versus high carotenoid intake and low alcohol or tobacco consumption ranged from 7 (95 % CI 5-9) to 33 (95 % CI 23-49). A diet rich in carotenoids may protect against HNC. Persons with both low carotenoid intake and high tobacco or alcohol are at substantially higher risk of HNC.
C1 [Leoncini, Emanuele; Boccia, Stefania] Univ Cattolica Sacro Cuore, Inst Publ Hlth, Sect Hyg, Largo F Vito 1, I-00168 Rome, Italy.
[Edefonti, Valeria; Ferraroni, Monica; Decarli, Adriano; La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Hashibe, Mia; Lee, Yuan-Chin Amy] Univ Utah, Sch Med, Dept Family & Prevent Med, Huntsman Canc Inst,Div Publ Hlth, Salt Lake City, UT 84112 USA.
[Parpinel, Maria] Univ Udine, Inst Hyg & Epidemiol, Dept Med & Biol Sci, I-33100 Udine, Italy.
[Cadoni, Gabriella] Univ Cattolica Sacro Cuore, Inst Otorhinolaryngol, Rome, Italy.
[Serraino, Diego] Aviano Canc Ctr, I-33081 Aviano, Italy.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Kyushu, Japan.
[Olshan, Andrew F.; Zevallos, Jose P.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Winn, Deborah M.] NCI, Bethesda, MD 20892 USA.
[Moysich, Kirsten] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Levi, Fabio] Univ Lausanne, CHU Vaudois, IUMSP, Lausanne, Switzerland.
[Kelsey, Karl] Brown Univ, Providence, RI 02912 USA.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Bosetti, Cristina] IRCCS Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
[Schantz, Stimson] New York Eye & Ear Infirm, New York, NY 10003 USA.
[Yu, Guo-Pei] Peking Univ, Med Informat Ctr, Beijing 100871, Peoples R China.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Chuang, Shu-Chun] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
RP Boccia, S (reprint author), Univ Cattolica Sacro Cuore, Inst Publ Hlth, Sect Hyg, Largo F Vito 1, I-00168 Rome, Italy.
EM sboccia@rm.unicatt.it
RI Parpinel, Maria/B-1605-2012; Decarli, Adriano/C-3129-2017; Ferraroni,
Monica/D-6548-2017; , emanuele/A-5466-2010
OI Matsuo, Keitaro/0000-0003-1761-6314; Serraino,
Diego/0000-0003-0565-8920; Parpinel, Maria/0000-0003-1309-4467; Decarli,
Adriano/0000-0003-1451-8292; Ferraroni, Monica/0000-0002-4542-4996; La
Vecchia, Carlo/0000-0003-1441-897X; EDEFONTI, VALERIA
CARLA/0000-0002-1995-1477; , emanuele/0000-0002-7669-8535
FU NIH (NCI) [R03CA113157]; NIH (NIDCR) [R03DE016611]; Italian Foundation
for Research on Cancer (Italian Ministry of Health, General Directorate
of European and International Relations); Italian Ministry of Education
[PRIN 2009 X8YCBN]; Italian Association for Research on Cancer (AIRC);
Italian League Against Cancer; Italian Ministry of Research; Swiss
League against Cancer; Swiss Research against Cancer/Oncosuisse
[KFS-700, OCS-1633]; National Institutes of Health (NIH) US
[R01CA078609, R01CA100679, R01CA061188]; National Institute of Health
(NIH) US [P50CA090388, R01DA011386, R03CA077954, T32CA009142,
U01CA096134, R21ES011667]; Alper Research Program for Environmental
Genomics of the UCLA Jonsson Comprehensive Cancer Center; National
Institute of Environmental Health Sciences [P30ES010126]; NCI, NIH,
United States; Ministry of Education, Science, Sports, Culture and
Technology of Japan [17015052]; Ministry of Health, Labor and Welfare of
Japan [H20-002]; Fondazione Veronesi; Italian Association for Research
on Cancer (AIRC) [10491 - 2010/2013]; NIH [R01CA051845]
FX The authors would like to thank all of the participants who took part in
this research for providing us very insightful and constructive
comments, which helped improve this manuscript. The INHANCE core data
pooling was supported by NIH Grants (NCI R03CA113157 and NIDCR
R03DE016611). The individual studies were supported by the following
grants: Milan study (2006-2009): Italian Foundation for Research on
Cancer (Italian Ministry of Health, General Directorate of European and
International Relations) and Italian Ministry of Education (PRIN 2009
X8YCBN). Italy Multicenter study: Italian Association for Research on
Cancer (AIRC), Italian League Against Cancer and Italian Ministry of
Research. Swiss study: Swiss League against Cancer and the Swiss
Research against Cancer/Oncosuisse (KFS-700, OCS-1633). Boston study:
National Institutes of Health (NIH) US (R01CA078609, R01CA100679). Los
Angeles study: National Institute of Health (NIH) US (P50CA090388,
R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667) and the
Alper Research Program for Environmental Genomics of the UCLA Jonsson
Comprehensive Cancer Center. MSKCC study: NIH (R01CA051845). North
Carolina (1994-1997): National Institutes of Health (NIH) US
(R01CA061188), and in part by a Grant from the National Institute of
Environmental Health Sciences (P30ES010126). US Multicenter study: The
Intramural Program of the NCI, NIH, United States. Japan (2001-2005):
Scientific Research Grant from the Ministry of Education, Science,
Sports, Culture and Technology of Japan (17015052) and Grant for the
Third-Term Comprehensive 10-year Strategy for Cancer Control from the
Ministry of Health, Labor and Welfare of Japan (H20-002). The work of EL
was supported by Fondazione Veronesi and Italian Association for
Research on Cancer (AIRC, Grant No. 10491 - 2010/2013).
NR 61
TC 0
Z9 0
U1 1
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
EI 1573-7284
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD APR
PY 2016
VL 31
IS 4
BP 369
EP 383
DI 10.1007/s10654-015-0036-3
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM9HC
UT WOS:000376675000004
PM 25930054
ER
PT J
AU Striegel, DA
Wojtowicz, D
Przytycka, TM
Periwal, V
AF Striegel, D. A.
Wojtowicz, D.
Przytycka, T. M.
Periwal, V.
TI Correlated rigid modes in protein families
SO PHYSICAL BIOLOGY
LA English
DT Article
DE protein families; normal modes; pattern recognition
ID ALLOSTERIC TRANSITIONS; BIOLOGICAL NANOMACHINES; SEQUENCE VARIATIONS;
EMPIRICAL BAYES; DYNAMICS; PATHWAYS; RESIDUES; ROBUST; CONFORMATIONS;
COMMUNICATION
AB A great deal of evolutionarily conserved information is contained in genomes and proteins. Enormous effort has been put into understanding protein structure and developing computational tools for protein folding, and many sophisticated approaches take structure and sequence homology into account. Several groups have applied statistical physics approaches to extracting information about proteins from sequences alone. Here, we develop a new method for sequence analysis based on first principles, in information theory, in statistical physics and in Bayesian analysis. We provide a complete derivation of our approach and we apply it to a variety of systems, to demonstrate its utility and its limitations. We show in some examples that phylogenetic alignments of amino-acid sequences of families of proteins imply the existence of a small number of modes that appear to be associated with correlated global variation. These modes are uncovered efficiently in our approach by computing a non-perturbative effective potential directly from the alignment. We show that this effective potential approaches a limiting form inversely with the logarithm of the number of sequences. Mapping symbol entropy flows along modes to underlying physical structures shows that these modes arise due to correlated compensatory adjustments. In the protein examples, these occur around functional binding pockets.
C1 [Striegel, D. A.; Periwal, V.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
[Wojtowicz, D.; Przytycka, T. M.] NCBI, Computat Biol Branch, NLM, NIH, Bethesda, MD 20892 USA.
RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM vipulp@mail.nih.gov
FU National Institutes of Health, NCBI; National Institutes of Health,
NIDDK
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NIDDK and NCBI. We are grateful to C Chow
and A Sherman for helpful discussions.
NR 48
TC 0
Z9 0
U1 3
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD APR
PY 2016
VL 13
IS 2
AR 025003
DI 10.1088/1478-3975/13/2/025003
PG 14
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DM5UJ
UT WOS:000376415400003
PM 27063781
ER
PT J
AU Striegel, DA
Hara, M
Periwal, V
AF Striegel, Deborah A.
Hara, Manami
Periwal, Vipul
TI Adaptation of pancreatic islet cyto-architecture during development
SO PHYSICAL BIOLOGY
LA English
DT Article
DE pancreatic islets; beta cells; cyto-architecture
ID INSULIN-SECRETION; BETA-CELLS; LANGERHANS; CONTACT; MICROANATOMY;
MODULATION; APOPTOSIS; RELEASE; ALPHA
AB Plasma glucose in mammals is regulated by hormones secreted by the islets of Langerhans embedded in the exocrine pancreas. Islets consist of endocrine cells, primarily alpha, beta, and delta cells, which secrete glucagon, insulin, and somatostatin, respectively. beta cells form irregular locally connected clusters within islets that act in concert to secrete insulin upon glucose stimulation. Varying demands and available nutrients during development produce changes in the local connectivity of beta cells in an islet. We showed in earlier work that graph theory provides a framework for the quantification of the seemingly stochastic cyto-architecture of beta cells in an islet. To quantify the dynamics of endocrine connectivity during development requires a framework for characterizing changes in the probability distribution on the space of possible graphs, essentially a Fokker-Planck formalism on graphs. With large-scale imaging data for hundreds of thousands of islets containing millions of cells from human specimens, we show that this dynamics can be determined quantitatively. Requiring that rearrangement and cell addition processes match the observed dynamic developmental changes in quantitative topological graph characteristics strongly constrained possible processes. Our results suggest that there is a transient shift in preferred connectivity for beta cells between 1-35 weeks and 12-24 months.
C1 [Striegel, Deborah A.; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Hara, Manami] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM vipulp@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, NIDDK
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, NIDDK. This study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health (http://hpc.nih.gov).
NR 36
TC 0
Z9 0
U1 4
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD APR
PY 2016
VL 13
IS 2
AR 025004
DI 10.1088/1478-3975/13/2/025004
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DM5UJ
UT WOS:000376415400004
PM 27063927
ER
PT J
AU Dao, P
Wojtowicz, D
Nelson, S
Levens, D
Przytycka, TM
AF Dao, Phuong
Wojtowicz, Damian
Nelson, Steevenson
Levens, David
Przytycka, Teresa M.
TI Ups and Downs of Poised RNA Polymerase II in B-Cells
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HYBRID G-QUADRUPLEX; C-MYC; POL-II;
DROSOPHILA-MELANOGASTER; TRANSCRIPTION INITIATION; GENE-TRANSCRIPTION;
PREPARES GENES; HUMAN GENOME; PROMOTERS
AB Recent genome-wide analyses have uncovered a high accumulation of RNA polymerase II (Pol II) at the 50 end of genes. This elevated Pol II presence at promoters, referred to here as Poll II poising, is mainly (but not exclusively) attributed to temporal pausing of transcription during early elongation which, in turn, has been proposed to be a regulatory step for processes that need to be activated "on demand". Yet, the full genome-wide regulatory role of Pol II poising is yet to be delineated. To elucidate the role of Pol II poising in B cell activation, we compared Pol II profiles in resting and activated B cells. We found that while Pol II poised genes generally overlap functionally among different B cell states and correspond to the functional groups previously identified for other cell types, non-poised genes are B cell state specific. Focusing on the changes in transcription activity upon B cell activation, we found that the majority of such changes were from poised to non-poised state. The genes showing this type of transition were functionally enriched in translation, RNA processing and mRNA metabolic process. Interestingly, we also observed a transition from non-poised to poised state. Within this set of genes we identified several Immediate Early Genes (IEG), which were highly expressed in resting B cell and shifted from non-poised to poised state after B cell activation. Thus Pol II poising does not only mark genes for rapid expression in the future, but it is also associated with genes that are silenced after a burst of their expression. Finally, we performed comparative analysis of the presence of G4 motifs in the context of poised versus non-poised but active genes. Interestingly we observed a differential enrichment of these motifs upstream versus downstream of TSS depending on poising status. The enrichment of G4 sequence motifs upstream of TSS of non-poised active genes suggests a potential role of quadruplexes in expression regulation.
C1 [Dao, Phuong; Wojtowicz, Damian; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Nelson, Steevenson] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Levens, David] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM przytyck@ncbi.nlm.nih.gov
FU National Library of Medicine, National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NAIMS); National Cancer Institute
(Center for Cancer Research) of the National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Library of Medicine, National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NAIMS), and the National Cancer
Institute (Center for Cancer Research) of the National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 60
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD APR
PY 2016
VL 12
IS 4
AR e1004821
DI 10.1371/journal.pcbi.1004821
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DM8BA
UT WOS:000376584400057
PM 27078128
ER
PT J
AU Maximova, T
Moffatt, R
Ma, BY
Nussinov, R
Shehu, A
AF Maximova, Tatiana
Moffatt, Ryan
Ma, Buyong
Nussinov, Ruth
Shehu, Amarda
TI Principles and Overview of Sampling Methods for Modeling Macromolecular
Structure and Dynamics
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Review
ID PROTEIN-STRUCTURE PREDICTION; INTRINSICALLY DISORDERED PROTEINS;
FREE-ENERGY LANDSCAPES; AMINO-ACID-SEQUENCE; NMR CHEMICAL-SHIFTS; MARKOV
STATE MODELS; ACCELERATED MOLECULAR-DYNAMICS; RESIDUAL DIPOLAR
COUPLINGS; LENNARD-JONES CLUSTERS; SIDE-CHAIN PREDICTION
AB Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.
C1 [Maximova, Tatiana; Moffatt, Ryan; Shehu, Amarda] George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA.
[Ma, Buyong; Nussinov, Ruth] Leidos Biomed Res Inc, Basic Sci Program, Canc & Inflammat Program, NCI, Frederick, MD USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
[Shehu, Amarda] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA.
[Shehu, Amarda] George Mason Univ, Sch Syst Biol, Manassas, VA USA.
RP Shehu, A (reprint author), George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA.; Nussinov, R (reprint author), Leidos Biomed Res Inc, Basic Sci Program, Canc & Inflammat Program, NCI, Frederick, MD USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.; Shehu, A (reprint author), George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA.; Shehu, A (reprint author), George Mason Univ, Sch Syst Biol, Manassas, VA USA.
EM nussinor@helix.nih.gov; amarda@gmu.edu
RI Ma, Buyong/F-9491-2011;
OI Ma, Buyong/0000-0002-7383-719X; Shehu, Amarda/0000-0001-5230-4610;
Maximova, Tatiana/0000-0002-5605-0678
FU National Science Foundation [1421001, 1440581, 1144106]; Thomas F. and
Kate Miller Jeffress Memorial Trust Award; NCI, NIH [HHSN261200800001E];
NIH, NCI, Center for Cancer Research
FX Funding for this work is provided in part by the National Science
Foundation (Grant No. 1421001, Grant No. 1440581, and CAREER Award No.
1144106 to AS) and the Thomas F. and Kate Miller Jeffress Memorial Trust
Award. This work has also been funded in whole or in part with Federal
funds from the NCI, NIH, under contract number HHSN261200800001E to BM
and RN. This study was supported (in part) by the Intramural Research
Program of the NIH, NCI, Center for Cancer Research. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 675
TC 10
Z9 10
U1 22
U2 45
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD APR
PY 2016
VL 12
IS 4
AR e1004619
DI 10.1371/journal.pcbi.1004619
PG 70
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DM8BA
UT WOS:000376584400042
PM 27124275
ER
PT J
AU Ruktanonchai, NW
DeLeenheer, P
Tatem, AJ
Alegana, VA
Caughlin, TT
Erbach-Schoenberg, EZ
Lourenco, C
Ruktanonchai, CW
Smith, DL
AF Ruktanonchai, Nick W.
DeLeenheer, Patrick
Tatem, Andrew J.
Alegana, Victor A.
Caughlin, T. Trevor
Erbach-Schoenberg, Elisabeth Zu
Lourenco, Christopher
Ruktanonchai, Corrine W.
Smith, David L.
TI Identifying Malaria Transmission Foci for Elimination Using Human
Mobility Data
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM TRANSMISSION; ANOPHELES MOSQUITOS; HUMAN MOVEMENT;
INFECTION; DYNAMICS; STRATEGIES; DISEASES; AFRICA; AREAS; SINKS
AB Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.
C1 [Ruktanonchai, Nick W.; Tatem, Andrew J.; Alegana, Victor A.; Erbach-Schoenberg, Elisabeth Zu; Lourenco, Christopher; Ruktanonchai, Corrine W.] Univ Southampton, WorldPop Project Geog & Environm, Southampton, Hants, England.
[Ruktanonchai, Nick W.; Tatem, Andrew J.; Alegana, Victor A.; Erbach-Schoenberg, Elisabeth Zu; Lourenco, Christopher; Ruktanonchai, Corrine W.] Flowminder Fdn, Stockholm, Sweden.
[DeLeenheer, Patrick] Oregon State Univ, Dept Math, Corvallis, OR 97331 USA.
[Caughlin, T. Trevor] Sch Forest Resources & Conservat, Gainesville, FL USA.
[Lourenco, Christopher] Clinton Hlth Access Initiat, Boston, MA USA.
[Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Smith, David L.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
[Smith, David L.] Univ Oxford, Dept Zool, Spatial Epidemiol & Evolut Grp, S Parks Rd, Oxford, England.
RP Ruktanonchai, NW (reprint author), Univ Southampton, WorldPop Project Geog & Environm, Southampton, Hants, England.; Ruktanonchai, NW (reprint author), Flowminder Fdn, Stockholm, Sweden.
EM nrukt00@gmail.com
OI Alegana, Victor/0000-0001-5177-9227
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; NIH/NIAID [U19AI089674]; Bill and Melinda Gates Foundation
[OPP1106427, 1032350]; Wellcome Trust Sustaining Health Grant
[106866/Z/15/Z]; National Science Foundation in the Quantitative Spatial
Ecology, Evolution and Environment Program at the University of Florida
[0801544]; Economic and Social Research Council's Doctoral Training
Center at the University of Southampton; National Science Foundation
Division of Mathematical Sciences [NSF-DMS-1411853]
FX AJT & DLS acknowledge funding support from the RAPIDD program of the
Science and Technology Directorate, Department of Homeland Security, and
the Fogarty International Center, National Institutes of Health, and are
also supported by grants from NIH/NIAID (U19AI089674) and the Bill and
Melinda Gates Foundation (OPP1106427 and #1032350). AJT also
acknowledges funding support from the Wellcome Trust Sustaining Health
Grant (106866/Z/15/Z). NWR acknowledges funding support from the
National Science Foundation under Grant No. 0801544 in the Quantitative
Spatial Ecology, Evolution and Environment Program at the University of
Florida. CWR acknowledges funding from the Economic and Social Research
Council's Doctoral Training Center at the University of Southampton. PD
acknowledges funding support in part from the National Science
Foundation Division of Mathematical Sciences (NSF-DMS-1411853). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 7
Z9 8
U1 4
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD APR
PY 2016
VL 12
IS 4
AR e1004846
DI 10.1371/journal.pcbi.1004846
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DM8BA
UT WOS:000376584400029
PM 27043913
ER
PT J
AU Chodick, G
Sigurdson, AJ
Kleinerman, RA
Sklar, CA
Leisenring, W
Mertens, AC
Stovall, M
Smith, SA
Weathers, RE
Veiga, LHS
Robison, LL
Inskip, PD
AF Chodick, Gabriel
Sigurdson, Alice J.
Kleinerman, Ruth A.
Sklar, Charles A.
Leisenring, Wendy
Mertens, Ann C.
Stovall, Marilyn
Smith, Susan A.
Weathers, Rita E.
Veiga, Lene H. S.
Robison, Leslie L.
Inskip, Peter D.
TI The Risk of Cataract among Survivors of Childhood and Adolescent Cancer:
A Report from the Childhood Cancer Survivor Study
SO RADIATION RESEARCH
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; IONIZING-RADIATION; OCULAR COMPLICATIONS;
UNITED-STATES; SURGERY; IRRADIATION; EXPOSURE; COHORT
AB With therapeutic successes and improved survival after a cancer diagnosis in childhood, increasing numbers of cancer survivors are at risk of subsequent treatment-related morbidities, including cataracts. While it is well known that the lens of the eye is one of the most radiosensitive tissues in the human body, the risks associated with radiation doses less than 2 Gy are less understood, as are the long-and short-term cataract risks from exposure to ionizing radiation at a young age. In this study, we followed 13,902 five-year survivors of childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.4 years from the date of first cancer diagnosis. For patients receiving radiotherapy, lens dose (mean: 2.2 Gy; range: 0-66 Gy) was estimated based on radiotherapy records. We used unconditional multivariable logistic regression models to evaluate prevalence of self-reported cataract in relationship to cumulative radiation dose both at five years after the initial cancer diagnosis and at the end of follow-up. We modeled the radiation effect in terms of the excess odds ratio (EOR) per Gy. We also analyzed cataract incidence starting from five years after initial cancer diagnosis to the end of follow-up using Cox regression. A total of 483 (3.5%) cataract cases were identified, including 200 (1.4%) diagnosed during the first five years of follow-up. In a multivariable logistic regression model, cataract prevalence at the end of follow-up was positively associated with lens dose in a manner consistent with a linear dose-response relationship (EOR per Gy = 0.92; 95% CI: 0.65-1.20). The odds ratio for doses between 0.5 and 1.5 Gy was elevated significantly relative to doses,0.5 Gy (OR = 2.2; 95% CI: 1.3-3.7). The results from this study indicate a strong association between ocular exposure to ionizing radiation and long-term risk of pre-senile cataract. The risk of cataract increased with increasing exposure, beginning at lens doses as low as 0.5 Gy. Our findings are in agreement with a growing body of evidence of an elevated risk for lens opacities in populations exposed to doses of ionizing radiation below the previously suggested threshold level of 2 Gy. (C) 2016 by Radiation Research Society
C1 [Chodick, Gabriel; Sigurdson, Alice J.; Kleinerman, Ruth A.; Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Chodick, Gabriel] Tel Aviv Univ, Fac Med, IL-69978 Tel Aviv, Israel.
[Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.
[Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Share Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Mertens, Ann C.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Stovall, Marilyn; Smith, Susan A.; Weathers, Rita E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Inst Radiat Protect & Dosimetry, Rio De Janeiro, Brazil.
[Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA.
RP Chodick, G (reprint author), Maccabi Healthcare Serv, Maccabitech, Hamered St 27, IL-6812509 Tel Aviv, Israel.
EM hodik_g@mac.org.il
FU Intramural Research Program of the National Cancer Institute (NCI)
Division of Cancer Epidemiology and Genetics (Bethesda, MD); Maccabi
Institute for Health Services Research (Tel Aviv, Israel); National
Cancer Institute [U24 CA55727]; American Lebanese Syrian Associated
Charities
FX This project would not have been possible without the generous
participation of the survivors who have contributed to the Childhood
Cancer Survivor Study (CCSS), as well as the efforts of the CCSS data
abstractors and survey interviewers. We thank the investigators of the
institutions that participated in the CCSS. This study was supported, in
part, by the Intramural Research Program of the National Cancer
Institute (NCI) Division of Cancer Epidemiology and Genetics (Bethesda,
MD) and the Maccabi Institute for Health Services Research (Tel Aviv,
Israel). The Childhood Cancer Survivor Study is supported by the
National Cancer Institute [grant no. U24 CA55727 (GT Armstrong,
Principal Investigator)] and funding from the American Lebanese Syrian
Associated Charities.
NR 41
TC 0
Z9 0
U1 0
U2 2
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD APR
PY 2016
VL 185
IS 4
BP 366
EP 374
DI 10.1667/RR14276.1
PG 9
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA DN0KG
UT WOS:000376752200004
PM 27023263
ER
PT J
AU Gadina, M
AF Gadina, Massimo
TI APPLIED CYTOKINE SIGNALING: FROM JAK INHIBITORS TO SUPER-ENHANCERS
SO RHEUMATOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the British-Society-for-Rheumatology,
British-Health-Professionals-in-Rheumatology and the
British-Society-for-Paediatric-and-Adolescent-Rheumatology
(Rheumatology)
CY APR 26-28, 2016
CL Glasgow, SCOTLAND
SP British Soc Rheumatol, British Hlth Profess Rheumatol, British Soc Paediat & Adolescent Rheumatol
C1 [Gadina, Massimo] NIAMSD, Translat Immunol Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD APR
PY 2016
VL 55
SU 1
MA I50
BP 11
EP 11
PG 1
WC Rheumatology
SC Rheumatology
GA DM9AO
UT WOS:000376656000041
ER
PT J
AU Reynolds, JA
Smith, CK
Sergeant, JC
Rosenberg, AZ
Rice, GI
Briggs, T
Bruce, IN
Kaplan, MJ
AF Reynolds, John A.
Smith, Carolyne K.
Sergeant, Jamie C.
Rosenberg, Avi Z.
Rice, Gillian I.
Briggs, Tracy
Bruce, Ian N.
Kaplan, Mariana J.
TI VITAMIN D DEFICIENCY PROMOTES VASCULAR DAMAGE AND DISEASE ACTIVITY IN A
MURINE MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS
SO RHEUMATOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the British-Society-for-Rheumatology,
British-Health-Professionals-in-Rheumatology and the
British-Society-for-Paediatric-and-Adolescent-Rheumatology
(Rheumatology)
CY APR 26-28, 2016
CL Glasgow, SCOTLAND
SP British Soc Rheumatol, British Hlth Profess Rheumatol, British Soc Paediat & Adolescent Rheumatol
C1 [Reynolds, John A.; Sergeant, Jamie C.; Briggs, Tracy; Bruce, Ian N.] Cent Manchester Univ Hosp NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester, Lancs, England.
[Reynolds, John A.; Smith, Carolyne K.; Kaplan, Mariana J.] NIAMSD, System Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Sergeant, Jamie C.] Univ Manchester, Ctr Musculoskeletal Res, Arthrit Res UK Ctr Epidemiol, Manchester, Lancs, England.
[Rosenberg, Avi Z.] Childrens Natl Med Ctr, Pathol, Washington, DC 20010 USA.
[Rosenberg, Avi Z.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Rice, Gillian I.] Univ Manchester, Genom Med, Inst Human Dev, Manchester, Lancs, England.
[Briggs, Tracy] Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Genet Med, Manchester, Lancs, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD APR
PY 2016
VL 55
SU 1
MA 269
BP 170
EP 170
PG 1
WC Rheumatology
SC Rheumatology
GA DM9AO
UT WOS:000376656000433
ER
PT J
AU Hajishengallis, G
Moutsopoulos, NM
Hajishengallis, E
Chavakis, T
AF Hajishengallis, George
Moutsopoulos, Niki M.
Hajishengallis, Evlambia
Chavakis, Triantafyllos
TI Immune and regulatory functions of neutrophils in inflammatory bone loss
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE Neutrophils; Inflammation; Bone loss; Periodontitis; Leukocyte-adhesion
deficiency; Del-1
ID LEUKOCYTE ADHESION DEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; GINGIVAL
CREVICULAR FLUID; LONG PENTRAXIN PTX3; PAPILLON-LEFEVRE-SYNDROME;
DEVELOPMENTAL ENDOTHELIAL LOCUS-1; COLONY-STIMULATING FACTOR;
GENOME-WIDE ASSOCIATION; CHRONIC PERIODONTITIS; PORPHYROMONAS-GINGIVALIS
AB Although historically viewed as merely anti-microbial effectors in acute infection or injury, neutrophils are now appreciated to be functionally versatile with critical roles also in chronic inflammation. Periodontitis, a chronic inflammatory disease that destroys the tooth-supporting gums and bone, is particularly affected by alterations in neutrophil numbers or function, as revealed by observations in monogenic disorders and relevant mouse models. Besides being a significant debilitating disease and health burden in its own right, periodontitis is thus an attractive model to dissect uncharted neutrophil-associated (patho)physiological pathways. Here, we summarize recent evidence that neutrophils can contribute to inflammatory bone loss not only through the typical bystander injury dogma but intriguingly also through their absence from the affected tissue, where they normally perform important immunomodulatory functions. Moreover, we discuss recent advances in the interactions of neutrophils with the vascular endothelium and - upon extravasation - with bacteria, and how the dysregulation of these interactions leads to inflammatory tissue damage. Overall, neutrophils have both protective and destructive roles in periodontitis, as they are involved in both the maintenance of periodontal tissue homeostasis and the induction of inflammatory bone loss. This highlights the importance of developing approaches that promote or sustain a fine balance between homeostatic immunity and inflammatory pathology. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Hajishengallis, George] Univ Penn, Dept Microbiol, Penn Dent Med, Philadelphia, PA 19104 USA.
[Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, NIH, Bethesda, MD 20892 USA.
[Hajishengallis, Evlambia] Univ Penn, Penn Dent Med, Dept Prevent & Restorat Sci, Div Pediat Dent, Philadelphia, PA 19104 USA.
[Chavakis, Triantafyllos] Tech Univ Dresden, Fac Med, Dept Clin Pathobiochem, D-01062 Dresden, Germany.
[Chavakis, Triantafyllos] Inst Clin Chem & Lab Med, Dresden, Germany.
RP Hajishengallis, G (reprint author), Univ Penn, Penn Dent Med, 240 South 40th St, Philadelphia, PA 19104 USA.
EM geoh@upenn.edu
FU Intramural Research Program of the NIH, NIDCR; European Community
[602699]; Else-Kroner-Fresenius-Stiftung [2014_A137]; U.S. Public Health
Service [AI068730, DE015254, DE017138, DE021685, DE024716]
FX The authors are supported by the following sources: The Intramural
Research Program of the NIH, NIDCR (N.M.M.); the European Community's
Seventh Framework Programme under grant agreement n602699 (DIREKT) and
the Else-Kroner-Fresenius-Stiftung (2014_A137) (TC); and by U.S. Public
Health Service grants AI068730 (E.H. and G.H.) and DE015254, DE017138,
DE021685, and DE024716 (GH). We thank Debbie Maizels (Zoobotanica
Scientific Illustration) for drawing Fig. 2 and Toshiharu Abe for help
with the drawing of Fig. 3.
NR 212
TC 8
Z9 8
U1 4
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD APR
PY 2016
VL 28
IS 2
BP 146
EP 158
DI 10.1016/j.smim.2016.02.002
PG 13
WC Immunology
SC Immunology
GA DM6OO
UT WOS:000376472500008
PM 26936034
ER
PT J
AU Vagida, MS
Arakelyan, A
Lebedeva, AM
Grivel, JC
Shpektor, AV
Vasilieva, EY
Margolis, LB
AF Vagida, M. S.
Arakelyan, A.
Lebedeva, A. M.
Grivel, J. -Ch.
Shpektor, A. V.
Vasilieva, E. Yu.
Margolis, L. B.
TI Analysis of extracellular vesicles using magnetic nanoparticles in blood
of patients with acute coronary syndrome
SO BIOCHEMISTRY-MOSCOW
LA English
DT Article
DE extracellular vesicles; platelets; acute coronary syndrome; flow
cytometry
ID ELEVATION MYOCARDIAL-INFARCTION; PLATELET-DERIVED MICROPARTICLES;
PATHOLOGICAL CONDITIONS; STABLE ANGINA; EXOSOMES; ATHEROTHROMBOSIS;
PATHOPHYSIOLOGY; ACTIVATION; DISEASE; CELLS
AB Extracellular vesicles (EVs) are released from various cell types and play an important role in intercellular interactions. In our study, we investigated abundance of individual EVs in patients with acute forms of ischemic heart disease. Previously, we developed an approach for individual analysis of EVs conjugated with magnetic nanoparticles (MNPs), which was applied in the current study for analyzing phenotypic composition of EVs (by staining for markers CD31, CD41a, and CD63). EVs were isolated using fluorescently labeled MNPs containing anti-CD31, CD41a, or CD63 antibodies and analyzed by combining fluorescently labeled anti-CD41a and CD63, CD31 and CD63, or CD41a and CD31 antibodies, respectively. EVs were analyzed in 30 individuals: 17 healthy volunteers and 13 patients with acute coronary syndrome (ACS). Six and seven ACS patients were with acute myocardial infarction and unstable angina, respectively. It was found that patients with ACS and healthy volunteers contained a dominant subset of EVs expressing surface CD41a antigen, suggesting that they originated from platelets. In addition, the total number of EVs isolated using either of the surface markers examined in our study was higher in patients with ACS compared to healthy volunteers. The subgroup of patients with acute myocardial infarction was found to contain significantly higher number of blood EVs compared to the control group. Moreover, increased number of EVs in patients with ACS is mainly due to the increased number of EVs in the subset of EVs bearing CD41a. By analyzing individual EVs, we found that plasma of patients with ACS, particularly upon developing of myocardial infarction, contained dominant platelet-derived EVs fraction, which may reflect activation of platelets in such patients.
C1 [Vagida, M. S.; Lebedeva, A. M.; Shpektor, A. V.; Vasilieva, E. Yu.] Moscow State Univ Med & Dent, Lab Atherothrombosis, Moscow 109240, Russia.
[Arakelyan, A.; Grivel, J. -Ch.; Margolis, L. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, NIH, Bethesda, MD 20892 USA.
RP Lebedeva, AM (reprint author), Moscow State Univ Med & Dent, Lab Atherothrombosis, Moscow 109240, Russia.
EM asya.lebedev@mail.ru
FU Government of the Russian Federation [14.B25.31.0016]
FX This study was financially supported by the Government of the Russian
Federation (project No. 14.B25.31.0016).
NR 44
TC 0
Z9 0
U1 2
U2 2
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0006-2979
EI 0320-9725
J9 BIOCHEMISTRY-MOSCOW+
JI Biochem.-Moscow
PD APR
PY 2016
VL 81
IS 4
BP 382
EP 391
DI 10.1134/S0006297916040088
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DM4FQ
UT WOS:000376302400008
PM 27293095
ER
PT J
AU Jaiswal, M
Fufaa, GD
Martin, CL
Pop-Busui, R
Nelson, RG
Feldman, EL
AF Jaiswal, Mamta
Fufaa, Gudeta D.
Martin, Catherine L.
Pop-Busui, Rodica
Nelson, Robert G.
Feldman, Eva L.
TI Burden of Diabetic Peripheral Neuropathy in Pima Indians With Type 2
Diabetes
SO DIABETES CARE
LA English
DT Letter
ID RISK-FACTORS; COMPLICATIONS
C1 [Jaiswal, Mamta; Feldman, Eva L.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA.
[Fufaa, Gudeta D.; Nelson, Robert G.] NIDDK, Phoenix, AZ USA.
[Martin, Catherine L.; Pop-Busui, Rodica] Univ Michigan, Dept Endocrinol, Ann Arbor, MI 48109 USA.
RP Feldman, EL (reprint author), Univ Michigan, Dept Neurol, Ann Arbor, MI USA.
EM efeldman@umich.edu
FU NIDDK NIH HHS [P30 DK020572]
NR 5
TC 1
Z9 1
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2016
VL 39
IS 4
BP E63
EP E64
DI 10.2337/dc16-0082
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DM3IP
UT WOS:000376240400006
PM 26908916
ER
PT J
AU Dohan, D
Garrett, SB
Rendle, KA
Halley, M
Abramson, C
AF Dohan, Daniel
Garrett, Sarah B.
Rendle, Katharine A.
Halley, Meghan
Abramson, Corey
TI The Importance Of Integrating Narrative Into Health Care Decision Making
SO HEALTH AFFAIRS
LA English
DT Article
ID MANAGEMENT RESEARCH; QUALITATIVE METHODS; SERVICES
AB When making health care decisions, patients and consumers use data but also gather stories from family and friends. When advising patients, clinicians consult the medical evidence but also use professional judgment. These stories and judgments, as well as other forms of narrative, shape decision making but remain poorly understood. Furthermore, qualitative research methods to examine narrative are rarely included in health science research. We illustrate how narratives shape decision making and explain why it is difficult but necessary to integrate qualitative research on narrative into the health sciences. We draw on social-scientific insights on rigorous qualitative research and our ongoing studies of decision making by patients with cancer, and we describe new tools and approaches that link qualitative research findings with the predominantly quantitative health science scholarship. Finally, we highlight the benefits of more fully integrating qualitative research and narrative analysis into the medical evidence base and into evidence-based medical practice.
C1 [Dohan, Daniel; Garrett, Sarah B.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Dohan, Daniel] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA.
[Rendle, Katharine A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Halley, Meghan] Palo Alto Med Fdn, Res Inst, Palo Alto, CA USA.
[Abramson, Corey] Univ Arizona, Sch Sociol, Tucson, AZ USA.
RP Dohan, D (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
EM daniel.dohan@ucsf.edu
FU Patient-Centered Outcomes Research Institute (PCORI) [ME-1409-22996];
National Cancer Institute (NCI) [NIH R01 CA152195]; Richard and Susan
Levy Fund
FX All authors were supported by the Patient-Centered Outcomes Research
Institute (PCORI; Grant No. ME-1409-22996; principal investigator:
Daniel Dohan). Additionally, Dohan, Sarah Garrett, and Corey Abramson
received support from the National Cancer Institute (NCI; Grant No. NIH
R01 CA152195; principal investigator: Dohan); and Meghan Halley received
support from the Richard and Susan Levy Fund. The authors thank Stuart
Henderson, Dominick Frosch, Suepattra May, and anonymous reviewers for
their helpful feedback. The authors are also deeply grateful to those
who participated in our studies of decision making and the experiences
of patients with cancer, on which the insights presented in this article
are based. The statements presented in this publication are solely the
responsibility of the authors and do not necessarily represent the views
of the National Institutes of Health or of PCORI, its Board of
Governors, or its Methodology Committee.
NR 23
TC 1
Z9 1
U1 5
U2 6
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD APR
PY 2016
VL 35
IS 4
BP 720
EP 725
DI 10.1377/hlthaff.2015.1373
PG 6
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DK2SG
UT WOS:000374764100023
PM 27044974
ER
PT J
AU Brenner, TA
Rice, TA
Anderson, ED
Percopo, CM
Rosenberg, HF
AF Brenner, Todd A.
Rice, Tyler A.
Anderson, Erik D.
Percopo, Caroline M.
Rosenberg, Helene F.
TI Immortalized MH-S cells lack defining features of primary alveolar
macrophages and do not support mouse pneumovirus replication
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE Macrophage; Inflammation; Siglec F; Pneumovirus; Pattern recognition
receptor; Granulocyte-macrophage colony stimulating factor
ID RESPIRATORY VIRUS-INFECTION; SIGLEC-F; PNEUMONIA VIRUS; GM-CSF;
LEGIONELLA-PNEUMOPHILA; FLOW-CYTOMETRY; IN-VITRO; MURINE; LINE;
EOSINOPHILS
AB The SV-40-transformed MH-S cell line maintains some, but not all, features of primary alveolar macrophages (AMs) from BALB/c mice. We show here that MH-S cells produce inflammatory cytokines IL-6 and CXCL10 in response to challenge with Gram-positive Lactobacillus reuteri, and to TLR2 and NOD2 ligands Pam3CSK4 and MDP, respectively. In contrast, although wild-type AMs are infected in vivo by pneumonia virus of mice (PVM), no virus replication was detected in MH-S cells. Interestingly, the surface immunophenotype of MH-S cells (CD11c(+)Siglec F-) differs from that of wild-type AMs (CD11c(+) Siglec F+) and is similar to that of immature AMs isolated from granulocyte macrophage-colony stimulating factor (GM-CSF) gene-deleted mice; AMs from GM-CSF-/- mice also support PVM replication. However, MH-S cells do not express the GM-CSF receptor alpha chain (CD116) and do not respond to GM-CSF. Due to these unusual features, MH-S cells should be used with caution as experimental models of AMs. Published by Elsevier B.V. on behalf of European Federation of Immunological Societies.
C1 [Brenner, Todd A.; Rice, Tyler A.; Anderson, Erik D.; Percopo, Caroline M.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
[Rice, Tyler A.] Yale Univ, Grad Dept Immunobiol, New Haven, CT USA.
RP Rosenberg, HF (reprint author), NIAID, IIS, LAD, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID Division of Intramural Research [AI000943]
FX The authors wish to thank Dr. Kimberly D. Dyer (IIS/LAD/NIAID) for her
advice on flow cytometry and use of the recombinant rK2-PVM virus. We
also thank Dr. Glenn Dranoff (Harvard University) for permission to use,
and Dr. Karen Elkins (FDA) and Dr. June Kwon-Chung (NIAID) for
assistance in obtaining the GM-CSF-/- gene-deleted mouse
strain. We also thank Dr. Rakesh Kumar, University of New South Wales,
Sydney, Australia, for sharing his experiences with the MH-S cell line.
This work was performed with support from the NIAID Division of
Intramural Research (AI000943 to HFR).
NR 52
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
EI 1879-0542
J9 IMMUNOL LETT
JI Immunol. Lett.
PD APR
PY 2016
VL 172
BP 106
EP 112
DI 10.1016/j.imlet.2016.02.012
PG 7
WC Immunology
SC Immunology
GA DM3AB
UT WOS:000376218100013
PM 26916143
ER
PT J
AU Chen, P
Urzua, CA
Knickelbein, JE
Kim, JS
Li, ZY
Hannes, S
Kuo, D
Chaigne-Delalande, B
Armbrust, K
Tucker, W
Liu, B
Agron, E
Sen, HN
Nussenblatt, RB
AF Chen, Ping
Urzua, Cristhian A.
Knickelbein, Jared E.
Kim, Jane S.
Li, Zhiyu
Hannes, Susan
Kuo, David
Chaigne-Delalande, Benjamin
Armbrust, Karen
Tucker, William
Liu, Baoying
Agron, Elvira
Sen, H. Nida
Nussenblatt, Robert B.
TI Elevated CD1c(+) Myeloid Dendritic Cell Proportions Associate With
Clinical Activity and Predict Disease Reactivation in Noninfectious
Uveitis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE CD1c(+) myeloid dendritic cells; noninfectious uveitis; clinical
activity; disease reactivation
ID RECURRENCE RATE; TH17 CELLS; GLUCOCORTICOIDS; EXPRESS; MDC1
AB PURPOSE. To test the association between elevated proportions of CD1c(+) myeloid dendritic cells (mDCs) and disease activation/reactivation in noninfectious uveitis.
METHODS. Noninfectious uveitis patients (n = 89) and healthy controls (n = 111) were recruited. The proportion of CD1c(+) mDCs in the total dendritic cell (DC) population of peripheral blood was measured by flow cytometry (CD1c(+) mDCs gated on Lineage 1(+)HLADR(+) DCs). Disease activity was assessed per Standardization of Uveitis Nomenclature criteria. Uveitis reactivation was ascribed to clinically quiescent patients who developed reactivation of intraocular inflammation within 6 months.
RESULTS. The proportions of CD1c(+) mDCs were increased in noninfectious uveitis patients, especially in active disease, compared to healthy controls. This CD1c(+) mDC elevation was not associated with underlying systemic diseases, anatomic locations of uveitis, medications, or demographic factors. Longitudinal data showed that the dynamics of CD1c(+) mDC levels were correlated with disease activity. The average proportion of CD1c(+) mDCs in active uveitis patients was 60% so we set this as the cutoff between high and low CD1c(+) mDC levels. Although 74% of quiescent patients had low proportions of CD1c(+) mDCs, 26% still had high proportions. Quiescent patients with high CD1c(+) mDC proportions showed increased risk of disease reactivation, compared to quiescent patients with low CD1c(+) mDC proportions.
CONCLUSIONS. Increased proportions of CD1c(+) mDCs were associated with clinical activity, and quiescent patients with elevated CD1c(+) mDCs were more likely to undergo reactivation. This suggests that CD1c(+) mDC proportion may be a potential biomarker for assessing clinical activation and reactivation in noninfectious uveitis.
C1 [Chen, Ping; Urzua, Cristhian A.; Knickelbein, Jared E.; Kim, Jane S.; Li, Zhiyu; Hannes, Susan; Kuo, David; Chaigne-Delalande, Benjamin; Armbrust, Karen; Tucker, William; Liu, Baoying; Sen, H. Nida; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Urzua, Cristhian A.] Univ Chile, Dept Ophthalmol, Santiago, Chile.
[Kim, Jane S.; Kuo, David] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
[Agron, Elvira] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM nussenblattr@nei.nih.gov
OI Armbrust, Karen/0000-0001-9381-4756
FU National Institutes of Health (NIH)/National Eye Institute (NEI); NIH
Medical Research Scholars Program; Pan-American Ophthalmological
Foundation/Retina Research Foundation; CONICYT
FX Supported by the Intramural Research Program of the National Institutes
of Health (NIH)/National Eye Institute (NEI). JSK and DK were supported
by the NIH Medical Research Scholars Program. CAU was supported by the
Pan-American Ophthalmological Foundation/Retina Research Foundation
(Guillingham fellowship) and the CONICYT (Becas Chile Program). The
authors alone are responsible for the content and writing of the paper.
NR 19
TC 1
Z9 1
U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2016
VL 57
IS 4
BP 1765
EP 1772
DI 10.1167/iovs.15-18357
PG 8
WC Ophthalmology
SC Ophthalmology
GA DL8XY
UT WOS:000375926700033
PM 27070110
ER
PT J
AU Ko, F
Boland, MV
Gupta, P
Gadkaree, SK
Vitale, S
Guallar, E
Zhao, D
Friedman, DS
AF Ko, Fang
Boland, Michael V.
Gupta, Priya
Gadkaree, Shekhar K.
Vitale, Susan
Guallar, Eliseo
Zhao, Di
Friedman, David S.
TI Diabetes, Triglyceride Levels, and Other Risk Factors for Glaucoma in
the National Health and Nutrition Examination Survey 2005-2008
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE glaucoma; glaucoma risk factors; NHANES
ID OPEN-ANGLE GLAUCOMA; NORMAL-TENSION GLAUCOMA; INTRAOCULAR-PRESSURE;
CIGARETTE-SMOKING; BLOOD-PRESSURE; METAANALYSIS; EYE; ASSOCIATION;
POPULATION; ONSET
AB PURPOSE. To determine risk factors for glaucoma in a population-based study in the United States.
METHODS. Participants age 40 and older from the National Health and Nutrition Examination Survey underwent questionnaires, physical examination, laboratory tests, and vision tests including fundus imaging. Glaucoma was determined based on expert grading of fundus photographs. Regression modeling of glaucoma risk factors was performed.
RESULTS. Participants with glaucoma (172) were older (mean age 68.1 [95% confidence interval (CI) 65.6-70.7] vs. 56.4 years [95% CI 55.6-57.2, P < 0.001]), likely to have less than high school education (25.1% vs. 18.1%, P = 0.05), to have diabetes (23.1% vs. 10.8%, P < 0.001), to have central obesity (72.5% vs. 60.7%, P = 0.01), to have systolic hypertension (30.3% vs. 20.1%, P = 0.01), to have diastolic hypotension (30.3% vs. 13.9%, P < 0.001), and to be nonsmokers (91.0% vs. 79.3%, P = 0.002). Sex, poverty, access to health care, fasting glucose, insulin dependence, body mass index, cholesterol levels, diastolic hypertension, systolic hypotension, obstructive sleep apnea, and marijuana were not associated with glaucoma. Multivariable modeling showed associations between glaucoma and older age (odds ratio [OR] 1.09 per year, 95% CI 1.04-1.14), black race (OR 4.40, 95% CI 1.71-11.30), and poverty (OR 3.39, 95% CI 1.73-6.66). Diabetes was no longer associated with glaucoma after adjustment for triglyceride levels. Sex, education, insurance status, body mass index, blood pressure, obstructive sleep apnea, and smoking were not associated with glaucoma.
CONCLUSIONS. People who are older, of black race, and with lower income levels have a higher prevalence of glaucoma. A novel association between diabetes, triglyceride levels, and glaucoma is also identified.
C1 [Ko, Fang] Moorfields Eye Hosp, Glaucoma, London, England.
[Boland, Michael V.; Friedman, David S.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Glaucoma Ctr Excellence, Baltimore, MD 21205 USA.
[Gupta, Priya] Surrey Eye Care Ctr, Surrey, BC, Canada.
[Gadkaree, Shekhar K.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Vitale, Susan] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Guallar, Eliseo; Zhao, Di] Johns Hopkins Univ, Sch Med, Welch Ctr Epidemiol, Baltimore, MD USA.
[Guallar, Eliseo; Zhao, Di; Friedman, David S.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21205 USA.
RP Friedman, DS (reprint author), Johns Hopkins Univ, 600 N Wolfe St,Wilmer 120, Baltimore, MD 21287 USA.
EM david.friedman@jhu.edu
FU National Institutes of Health [EY01766]; Research to Prevent Blindness
FX Research at the Wilmer Eye Institute is supported by National Institutes
of Health Grant EY01766 and by a grant from Research to Prevent
Blindness. The funding agencies had no role in the design or conduct of
this research.
NR 30
TC 2
Z9 2
U1 1
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD APR
PY 2016
VL 57
IS 4
BP 2152
EP 2157
DI 10.1167/iovs.15-18373
PG 6
WC Ophthalmology
SC Ophthalmology
GA DL8XY
UT WOS:000375926700068
PM 27111561
ER
PT J
AU Chomistek, AK
Shiroma, EJ
Lee, IM
AF Chomistek, Andrea K.
Shiroma, Eric J.
Lee, I-Min
TI The Relationship Between Time of Day of Physical Activity and Obesity in
Older Women
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE exercise; accelerometry; overweight; epidemiology
ID PREVENTION; PATTERNS; BEHAVIOR
AB Background: Physical activity is important for maintaining healthy weight. The time of day when exercise is performed a highly discretionary aspect of behavior may impact weight control, but evidence is limited. Thus, we examined the association between the timing of physical activity and obesity risk in women. Methods: A cross-sectional analysis was conducted among 7157 Women's Health Study participants who participated in an ancillary study begun in 2011 that is measuring physical activity using accelerometers. The exposure was percentage of total accelerometer counts accumulated before 12:00 noon and the outcome was obesity. Results: Mean (+/- SD) BMI among participants was 26.1 (+/- 4.9) kg/m(2) and 1322 women were obese. The mean activity counts per day was 203,870 (95,811) of which a mean 47.1% (+/- 11.5%) were recorded in the morning. In multivariable-adjusted models, women who recorded < 39% (lowest quartile) of accelerometer counts before 12:00 noon had a 26% higher odds of being obese, compared with those recording >= 54% (highest quartile) of counts before noon (P-trend = 0.02). Conclusions: These study findings-that women who are less active during morning hours may be at higher risk of obesity-if confirmed can provide a novel strategy to help combat the important health problem of obesity.
C1 [Chomistek, Andrea K.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.
[Shiroma, Eric J.] NIA, NIH, Bethesda, MD 20892 USA.
[Lee, I-Min] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA.
RP Chomistek, AK (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.
EM achomist@indiana.edu
RI Chomistek, Andrea/A-2104-2017
OI Chomistek, Andrea/0000-0002-8764-1446
FU National Institutes of Health [CA154647, CA047988, HL043851, HL080467,
HL099355]
FX We are grateful to the staff of the Women's Health Study (Brigham and
Women's Hospital), particularly Ara Sarkissian, MM, Bonnie Church, BA,
Colby Smith, BS, and Jane Jones, MEd as well as Dr. Patty Freedson, PhD.
This research was supported by research grants CA154647, CA047988,
HL043851, HL080467, and HL099355 from the National Institutes of Health.
NR 14
TC 1
Z9 1
U1 0
U2 1
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD APR
PY 2016
VL 13
IS 4
BP 416
EP 418
DI 10.1123/jpah.2015-0152
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM3BG
UT WOS:000376221200009
PM 26445277
ER
PT J
AU Baba, M
Toyama, H
Sun, L
Takubo, K
Suh, HC
Hasumi, H
Nakamura-Ishizu, A
Hasumi, Y
Klarmann, KD
Nakagata, N
Schmidt, LS
Linehan, WM
Suda, T
Keller, JR
AF Baba, Masaya
Toyama, Hirofumi
Sun, Lei
Takubo, Keiyo
Suh, Hyung-Chan
Hasumi, Hisashi
Nakamura-Ishizu, Ayako
Hasumi, Yukiko
Klarmann, Kimberly D.
Nakagata, Naomi
Schmidt, Laura S.
Linehan, W. Marston
Suda, Toshio
Keller, Jonathan R.
TI Loss of Folliculin Disrupts Hematopoietic Stem Cell Quiescence and
Homeostasis Resulting in Bone Marrow Failure
SO STEM CELLS
LA English
DT Article
DE Hematopoiesis; Stem cells; Bone marrow failure; Folliculin
ID BIRT-HOGG-DUBE; TUMOR-SUPPRESSOR FUNCTION; SIGNALING PATHWAYS;
POLYCYSTIC KIDNEYS; MTOR ACTIVATION; CRITICAL ROLES; PROTEIN; PTEN;
FLCN; TRANSCRIPTION
AB Folliculin (FLCN) is an autosomal dominant tumor suppressor gene that modulates diverse signaling pathways required for growth, proliferation, metabolism, survival, motility, and adhesion. FLCN is an essential protein required for murine embryonic development, embryonic stem cell (ESC) commitment, and Drosophila germline stem cell maintenance, suggesting that Flcn may be required for adult stem cell homeostasis. Conditional inactivation of Flcn in adult hematopoietic stem/progenitor cells (HSPCs) drives hematopoietic stem cells (HSC) into proliferative exhaustion resulting in the rapid depletion of HSPC, loss of all hematopoietic cell lineages, acute bone marrow (BM) failure, and mortality after 40 days. HSC that lack Flcn fail to reconstitute the hematopoietic compartment in recipient mice, demonstrating a cell-autonomous requirement for Flcn in HSC maintenance. BM cells showed increased phosphorylation of Akt and mTorc1, and extramedullary hematopoiesis was significantly reduced by treating mice with rapamycin in vivo, suggesting that the mTorc1 pathway was activated by loss of Flcn expression in hematopoietic cells in vivo. Tfe3 was activated and preferentially localized to the nucleus of Flcn knockout (KO) HSPCs. Tfe3 overexpression in HSPCs impaired long-term hematopoietic reconstitution in vivo, recapitulating the Flcn KO phenotype, and supporting the notion that abnormal activation of Tfe3 contributes to the Flcn KO phenotype. Flcn KO mice develop an acute histiocytic hyperplasia in multiple organs, suggesting a novel function for Flcn in macrophage development. Thus, Flcn is intrinsically required to maintain adult HSC quiescence and homeostasis, and Flcn loss leads to BM failure and mortality in mice. Stem Cells2016;34:1068-1082
C1 [Baba, Masaya; Hasumi, Hisashi; Hasumi, Yukiko; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Baba, Masaya; Suda, Toshio] Kumamoto Univ, IRCMS, Kumamoto, Japan.
[Toyama, Hirofumi; Takubo, Keiyo; Nakamura-Ishizu, Ayako; Suda, Toshio] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab Dev Biol,Shinjuku Ku, 35 Shinano Machi, Tokyo, Japan.
[Sun, Lei; Suh, Hyung-Chan; Klarmann, Kimberly D.; Keller, Jonathan R.] Mouse Canc Genet Program, Frederick, MD USA.
[Sun, Lei; Suh, Hyung-Chan; Klarmann, Kimberly D.; Schmidt, Laura S.; Keller, Jonathan R.] Leidos Biomed Res Inc, Basic Sci Program, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Takubo, Keiyo] Natl Ctr Global Hlth & Med, Dept Stem Cell Biol, Res Inst, Tokyo, Japan.
[Nakagata, Naomi] Kumamoto Univ, Div Reprod Engn, CARD, Kumamoto, Japan.
[Nakamura-Ishizu, Ayako; Suda, Toshio] Natl Univ Singapore, CSI, Singapore 117548, Singapore.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.; Suda, T (reprint author), Kumamoto Univ, IRCMS, Kumamoto, Japan.; Keller, JR (reprint author), Leidos Biomed Res Inc, Basic Sci Program, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM linehanm@mail.nih.gov; sudato@z3.keio.jp; kellerjo@mail.nih.gov
FU National Institutes of Health (NIH), National Cancer Institute (NCI);
Center for Cancer Research; Keio University; BioLegend/Tomy Digital
Biology Research Grant Program; JSPS KAKENHI; JSPS KAKENHI [15H04975,
15K14370]; Frederick National Laboratory for Cancer Research, NIH
[HHSN261200800001E]
FX We wish to thank Steven Stull, Terri Stull, and Louise Cromwell for
excellent animal technical support. This work was supported by the
Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute (NCI), and Center for Cancer Research, and by
Keio University Grant-in-Aid for Encouragement of Young Medical
Scientists, by BioLegend/Tomy Digital Biology Research Grant Program
2013 (Latter Term). T.S. and M.B. were supported in part by a JSPS
KAKENHI Grant-in-Aid for Scientific Research (S). M.B. was supported by
JSPS KAKENHI, Grant-in-Aid for Scientific Research (B), Grant Number
15H04975; and Grant-in-Aid for Challenging Exploratory Research, Grant
Number 15K14370. This project has been funded in part with Federal funds
from the Frederick National Laboratory for Cancer Research, NIH, under
Contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsements by the US Government.
NCI-Frederick is accredited by AAALAC International and follows the
Public Health Service Policy for the Care and Use of Laboratory Animals.
Animal care was provided in accordance with the procedures outlined in
the "Guide for Care and Use of Laboratory Animals" (National Research
Council; 1996; National Academy Press; Washington DC).
NR 43
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD APR
PY 2016
VL 34
IS 4
BP 1068
EP 1082
DI 10.1002/stem.2293
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA DK1TR
UT WOS:000374697700022
PM 27095138
ER
PT J
AU Agbor-Enoh, S
Tunc, I
Doveikis, J
Khush, K
De Vlaminck, I
Davis, A
Wang, X
Solomon, MA
Zhu, J
Valantine, HA
AF Agbor-Enoh, S.
Tunc, I.
Doveikis, J.
Khush, K.
De Vlaminck, I.
Davis, A.
Wang, X.
Solomon, M. A.
Zhu, J.
Valantine, H. A.
TI Reproducibility of Genomic Data Using Standards-Cell Free DNA to Monitor
Rejection after Heart Transplantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Agbor-Enoh, S.; Tunc, I.; Doveikis, J.; Davis, A.; Wang, X.; Solomon, M. A.; Zhu, J.; Valantine, H. A.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Khush, K.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[De Vlaminck, I.] Cornell Univ, Ithaca, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 421
BP S161
EP S161
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718100418
ER
PT J
AU Agbor-Enoh, S
Fideli, U
Doveikis, J
Zhu, J
Tunc, I
Shah, P
Russell, S
Feller, E
Shah, K
Rodrigo, M
Shah, P
Pham, S
Iacono, A
Nathan, S
Orens, J
Valantine, H
AF Agbor-Enoh, S.
Fideli, U.
Doveikis, J.
Zhu, J.
Tunc, I.
Shah, P.
Russell, S.
Feller, E.
Shah, K.
Rodrigo, M.
Shah, P.
Pham, S.
Iacono, A.
Nathan, S.
Orens, J.
Valantine, H.
CA N GRAfT Investigators
TI Genomic Research Alliance for Transplantation (GRAfT): A Model for Long
Term Transplant Studies in Thoracic Organ Transplantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Agbor-Enoh, S.; Fideli, U.; Doveikis, J.; Zhu, J.; Tunc, I.; Valantine, H.; N GRAfT Investigators] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Shah, P.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Russell, S.] Johns Hopkins Univ Hosp, Cardiol, Baltimore, MD 21287 USA.
[Feller, E.] Univ Maryland, Med Ctr, Cadiol, Baltimore, MD 21201 USA.
[Shah, K.] Virginia Commonwealth Univ, Cardiol, Richmond, VA USA.
[Rodrigo, M.] Medstar Washington Hosp Ctr, Cardiol, Washington, DC USA.
[Shah, P.] INOVA Fairfax Hosp, Cardiol, Fairfax, VA USA.
[Pham, S.] Univ Maryland, Med Ctr, Cadiothorac Surg, Baltimore, MD 21201 USA.
[Iacono, A.] Univ Maryland, Med Ctr, Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Nathan, S.] INOVA Fairfax Hosp, Pulm & Crit Care Med, Fairfax, VA USA.
[Orens, J.] Johns Hopkins Univ Hosp, Pulm & Crit Care Med, Baltimore, MD 21287 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 422
BP S161
EP S161
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718100419
ER
PT J
AU Zhao, XZ
Smith, SJ
Maskell, DP
Metifiot, M
Pye, VE
Fesen, K
Marchand, C
Pommier, Y
Cherepanov, P
Hughes, SH
Burke, TR
AF Zhao, Xue Zhi
Smith, Steven J.
Maskell, Daniel P.
Metifiot, Mathieu
Pye, Valerie E.
Fesen, Katherine
Marchand, Christophe
Pommier, Yves
Cherepanov, Peter
Hughes, Stephen H.
Burke, Terrence R., Jr.
TI HIV-1 Integrase Strand Transfer Inhibitors with Reduced Susceptibility
to Drug Resistant Mutant Integrases
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID CROSS-RESISTANCE; RALTEGRAVIR; DOLUTEGRAVIR; ELVITEGRAVIR; DERIVATIVES;
MECHANISMS; MUTATIONS; EVOLUTION; INFECTION; FREQUENCY
AB HIV integrase (IN) strand transfer inhibitors (INSTIs) are among the newest anti-AIDS drugs; however, mutant forms of IN can confer resistance. We developed noncytotoxic naphthyridine-containing INSTIs that retain low nanomolar IC50 values against HIV-1 variants harboring all of the major INSTI-resistant mutations. We found by analyzing crystal structures of inhibitors bound to the IN from the prototype foamy virus (PFV) that the most successful inhibitors show striking mimicry of the bound viral DNA prior to 3'-processing and the bound host DNA prior to strand transfer. Using this concept of "bi-substrate mimicry," we developed a new broadly effective inhibitor that not only mimics aspects of both the bound target and viral DNA but also more completely fills the space they would normally occupy. Maximizing shape complementarity and recapitulating structural components encompassing both of the IN DNA substrates could serve as a guiding principle for the development of new INSTIs.
C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Chem Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Smith, Steven J.] NCI, HIV Dynam & Replicat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Metifiot, Mathieu; Fesen, Katherine; Marchand, Christophe; Pommier, Yves; Hughes, Stephen H.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Metifiot, Mathieu; Fesen, Katherine; Marchand, Christophe; Pommier, Yves; Hughes, Stephen H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Maskell, Daniel P.; Pye, Valerie E.; Cherepanov, Peter] Francis Crick Inst, Clare Hall Labs, Blanche Lane, S Mimms EN6 3LD, Herts, England.
[Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, St Marys Campus,Norfolk Pl, London W2 1PG, England.
RP Burke, TR (reprint author), NCI, Chem Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM burkete@helix.nih.gov
RI Cherepanov, Peter/F-6859-2010;
OI Cherepanov, Peter/0000-0002-0634-538X; Pye, Valerie
E/0000-0001-9616-2992
FU NIH Intramural Program, Center for Cancer Research, National Cancer
Institute [ZIA BC 007363, Z01 BC 007333]; NIH Intramural AIDS Targeted
Antiviral Program (IATAP)
FX We thank the staff of the Diamond Light Source beamline I04 for
assistance with X-ray data collection. Our studies are supported by the
NIH Intramural Program, Center for Cancer Research (ZIA BC 007363, Z01
BC 007333), National Cancer Institute and by grants from the NIH
Intramural AIDS Targeted Antiviral Program (IATAP).
NR 43
TC 4
Z9 4
U1 3
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD APR
PY 2016
VL 11
IS 4
BP 1074
EP 1081
DI 10.1021/acschembio.5b00948
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ8BL
UT WOS:000374437000028
PM 26808478
ER
PT J
AU Dankwa-Mullan, I
Perez-Stable, EJ
AF Dankwa-Mullan, Irene
Perez-Stable, Eliseo J.
TI Addressing Health Disparities Is a Place-Based Issue
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Dankwa-Mullan, Irene] Natl Inst Minor Hlth & Hlth Dispar, Div Sci Programs, NIH, Bethesda, MD USA.
[Perez-Stable, Eliseo J.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA.
RP Perez-Stable, EJ (reprint author), 6707 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
EM eliseo.perez-stable@nih.gov
NR 9
TC 2
Z9 2
U1 0
U2 4
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD APR
PY 2016
VL 106
IS 4
BP 637
EP 639
DI 10.2105/AJPH.2016.303077
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DL8SY
UT WOS:000375913000024
PM 26959267
ER
PT J
AU Jones, CM
Lurie, PG
Compton, WM
AF Jones, Christopher M.
Lurie, Peter G.
Compton, Wilson M.
TI Increase in Naloxone Prescriptions Dispensed in US Retail Pharmacies
Since 2013
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
AB Distribution of naloxone, traditionally through community-based naloxone programs, is a component of a comprehensive strategy to address the epidemic of prescription opioid and heroin overdose deaths in the United States. Recently, there has been increased focus on naloxone prescription in the outpatient setting, particularly through retail pharmacies, yet data on this practice are sparse. We found an 1170% increase in naloxone dispensing from US retail pharmacies between the fourth quarter of 2013 and the second quarter of 2015. These findings suggest that prescribing naloxone in the outpatient setting complements traditional community-based naloxone programs.
C1 [Jones, Christopher M.] US Dept Hlth & Human Serv, Off Assistant Secretary Planning & Evaluat, Div Sci Policy, 200 Independence Ave SW, Washington, DC 20201 USA.
[Lurie, Peter G.] US FDA, Off Publ Hlth Strategy & Anal, Silver Spring, MD USA.
[Compton, Wilson M.] NIDA, NIH, Rockville, MD USA.
RP Jones, CM (reprint author), US Dept Hlth & Human Serv, Off Assistant Secretary Planning & Evaluat, Div Sci Policy, 200 Independence Ave SW, Washington, DC 20201 USA.
EM christopher.m.jones@fda.hhs.gov
NR 8
TC 5
Z9 5
U1 1
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD APR
PY 2016
VL 106
IS 4
BP 689
EP 690
DI 10.2105/AJPH.2016.303062
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DL8SY
UT WOS:000375913000036
PM 26890174
ER
PT J
AU Kuijpers, E
Bekker, C
Fransman, W
Brouwer, D
Tromp, P
Vlaanderen, J
Godderis, L
Hoet, P
Lan, Q
Silverman, D
Vermeulen, R
Pronk, A
AF Kuijpers, Eelco
Bekker, Cindy
Fransman, Wouter
Brouwer, Derk
Tromp, Peter
Vlaanderen, Jelle
Godderis, Lode
Hoet, Peter
Lan, Qing
Silverman, Debra
Vermeulen, Roel
Pronk, Anjoeka
TI Occupational Exposure to Multi-Walled Carbon Nanotubes During Commercial
Production Synthesis and Handling
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE Commercial production; multi-walled carbon nanotubes; occupational
exposure
ID ASSESSMENT TECHNIQUE NEAT; INHALATION EXPOSURE; NANO-OBJECTS;
NANOMATERIALS; PARTICLES; RELEASE; IDENTIFICATION; COMPOSITES;
SCENARIOS; FIBERS
AB The world-wide production of carbon nanotubes (CNTs) has increased substantially in the last decade, leading to occupational exposures. There is a paucity of exposure data of workers involved in the commercial production of CNTs. The goals of this study were to assess personal exposure to multi-walled carbon nanotubes (MWCNTs) during the synthesis and handling of MWCNTs in a commercial production facility and to link these exposure levels to specific activities. Personal full-shift filter-based samples were collected, during commercial production and handling of MWCNTs, R&D activities, and office work. The concentrations of MWCNT were evaluated on the basis of EC concentrations. Associations were studied between observed MWCNT exposure levels and location and activities. SEM analyses showed MWCNTs, present as agglomerates ranging between 200nm and 100 A mu m. Exposure levels of MWCNTs observed in the production area during the full scale synthesis of MWCNTs (N = 23) were comparable to levels observed during further handling of MWCNTs (N = 19): (GM (95% lower confidence limit-95% upper confidence limit)) 41 mu g m(-3) (20-88) versus 43 mu g m(-3) (22-86), respectively. In the R&D area (N = 11) and the office (N = 5), exposure levels of MWCNTs were significantly (P < 0.05) lower: 5 mu g m(-3) (2-11) and 7 mu g m(-3) (2-28), respectively. Bagging, maintenance of the reactor, and powder conditioning were associated with higher exposure levels in the production area, whereas increased exposure levels in the R&D area were related to handling of MWCNTs powder.
C1 [Kuijpers, Eelco; Bekker, Cindy; Fransman, Wouter; Brouwer, Derk; Tromp, Peter; Pronk, Anjoeka] TNO, POB 360, Zeist, Netherlands.
[Bekker, Cindy; Vlaanderen, Jelle; Vermeulen, Roel] IRAS, Inst Risk Assessment Sci Mol Epidemiol & Risk Ass, Yalelaan 1, NL-3584 CL Utrecht, Netherlands.
[Godderis, Lode; Hoet, Peter] Katholieke Univ Leuven, Ctr Environm & Hlth, Kapucijnenvoer 35-5, B-3000 Louvain, Belgium.
[Godderis, Lode] IDEWE, External Serv Prevent & Protect Work, Interleuvenlaan 58, B-3001 Heverlee, Belgium.
[Lan, Qing; Silverman, Debra] Natl Canc Inst, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Executive Blvd, Bethesda, MD USA.
RP Kuijpers, E (reprint author), TNO, POB 360, Zeist, Netherlands.
EM eelco.kuijpers@tno.nl
RI Vermeulen, Roel/F-8037-2011; Hoet, Peter/H-9987-2013
OI Vermeulen, Roel/0000-0003-4082-8163; Hoet, Peter/0000-0002-0292-6603
FU NanoNextNL; micro and nanotechnology consortium of the Government of the
Netherlands; 130 partners
FX The research was partly funded by NanoNextNL, a micro and nanotechnology
consortium of the Government of the Netherlands and 130 partners. The
paper was reviewed by the funder and studied company prior to
submission. We thank Roel Engel, Ruud Boessen and the supportive studied
company for their contributions. None of the authors has a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript.
NR 42
TC 2
Z9 2
U1 3
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD APR
PY 2016
VL 60
IS 3
BP 305
EP 317
DI 10.1093/annhyg/mev082
PG 13
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA DJ5FY
UT WOS:000374233400005
PM 26613611
ER
PT J
AU Xu, L
Verdoodt, F
Wentzensen, N
Bergeron, C
Arbyn, M
AF Xu, Lan
Verdoodt, Freija
Wentzensen, Nicolas
Bergeron, Christine
Arbyn, Marc
TI Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV
testing and other markers to detect cervical precancer
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE atypical squamous cells; cannot exclude high-grade squamous
intraepithelial lesion (ASC-H); cervical cancer; cervical
intraepithelial neoplasia; diagnostic test accuracy; human
papillomavirus (HPV); meta-analysis; triage
ID ATYPICAL SQUAMOUS-CELLS; PATHOLOGY SCREENING GUIDELINES;
HUMAN-PAPILLOMAVIRUS GENOTYPES; GRADE INTRAEPITHELIAL LESION;
AMERICAN-CANCER-SOCIETY; HYBRID-CAPTURE-II; FOLLOW-UP; 5-YEAR RISKS;
UNDETERMINED SIGNIFICANCE; DIAGNOSTIC PERFORMANCE
AB BACKGROUNDWomen with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment.
METHODSA meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer.
RESULTSThe pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2+(derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2+and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively.
CONCLUSIONSBecause of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral. Cancer Cytopathol 2016;124:261-72. (c) 2015 American Cancer Society.
Because of the high probability of precancer in patients with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), the utility of triage is limited. The usual recommendation of referring women with ASC-H to colposcopy is not altered by a positive triage test, whatever test is used. A negative high-risk human papillomavirus DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.
C1 [Xu, Lan; Verdoodt, Freija; Arbyn, Marc] Sci Inst Publ Hlth, Canc Epidemiol Unit, Belgian Canc Ctr, Juliette Wytsmanstr 14, B-1050 Brussels, Belgium.
[Verdoodt, Freija] Danish Canc Soc, Res Ctr, Unit Virus Lifestyle & Genes, Copenhagen, Denmark.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Bergeron, Christine] Lab Cerba, Cergy Pontoise, France.
RP Arbyn, M (reprint author), Sci Inst Publ Hlth, Canc Epidemiol Unit, Belgian Canc Ctr, Juliette Wytsmanstr 14, B-1050 Brussels, Belgium.
EM marc.arbyn@wiv-isp.be
FU Directorate-General for Research of the European Commission through the
comparing health services interventions for the prevention of
HPV-related cancer (COHEAHR) network [603019]; German Guideline Program
in Oncology (German Cancer Aid project) [110163]; Joint Action on
Comprehensive Cancer Control; European Union
FX Marc Arbyn, Lan Xu, and Freija Verdoodt were supported by the Seventh
Framework Program of the Directorate-General for Research of the
European Commission through the comparing health services interventions
for the prevention of HPV-related cancer (COHEAHR) network (grant
603019). Other funding was received from the German Guideline Program in
Oncology (German Cancer Aid project 110163). Marc Arbyn's work was
supported by the Joint Action on Comprehensive Cancer Control, which has
received funding from the European Union within the framework of the
Health Programme (2008-2013).
NR 60
TC 5
Z9 5
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD APR
PY 2016
VL 124
IS 4
BP 261
EP 272
DI 10.1002/cncy.21661
PG 12
WC Oncology; Pathology
SC Oncology; Pathology
GA DJ6QQ
UT WOS:000374338400007
PM 26618614
ER
PT J
AU Davis, FM
Goulding, EH
D'Agostin, DM
Janardhan, KS
Cummings, CA
Bird, GS
Eddy, EM
Putney, JW
AF Davis, Felicity M.
Goulding, Eugenia H.
D'Agostin, Diane M.
Janardhan, Kyathanahalli S.
Cummings, Connie A.
Bird, Gary S.
Eddy, Edward M.
Putney, James W.
TI Male infertility in mice lacking the store-operated Ca2+ channel Orai1
SO CELL CALCIUM
LA English
DT Article
DE Ca2+; Orai1; Store-operated calcium entry (SOCE); Reproduction;
Fertility; Spermatogenesis
ID CALCIUM-CHANNELS; MALE-FERTILITY; EGG ACTIVATION; ION CHANNELS; HUMAN
SPERM; CELLS; ENTRY; STIM1; GENE; PROGESTERONE
AB Store-operated calcium entry (SOCE) is an important Ca2+ influx pathway in somatic cells. In addition to maintaining endoplasmic reticulum (ER) Ca2+ stores, Ca2+ entry through store-operated channels regulates essential signaling pathways in numerous cell types. Patients with mutations in the store-operated channel subunit ORAI1 exhibit defects in store-operated Ca2+ influx, along with severe immunodeficiency, congenital myopathy and ectodermal dysplasia. However, little is known about the functional role of ORAI1 in germ cells and reproductive function in mice, or in men, since men with loss-of-function or null mutations in ORAI1 rarely survive to reproductive age. In this study, we investigated the role of ORAI1 in male reproductive function. We reveal that Orai1(-/-) male mice are sterile and have severe defects in spermatogenesis, with prominent deficiencies in mid- to late-stage elongating spermatid development. These studies establish an essential in vivo role for store-operated ORAI1 channels in male reproductive function and identify these channels as potential non-steroidal regulators of male fertility. Published by Elsevier Ltd.
C1 [Davis, Felicity M.; D'Agostin, Diane M.; Bird, Gary S.; Putney, James W.] NIEHS, Signal Transduct Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Goulding, Eugenia H.; Eddy, Edward M.] NIEHS, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli S.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA.
[Cummings, Connie A.] UltraPath Imaging, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), NIEHS, Signal Transduct Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov
RI Davis, Felicity/P-1387-2016
OI Davis, Felicity/0000-0001-9112-118X
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX We thank John Brodie, Agnes Janoshazi, Page Myers, Pamela Ovwigho,
Deloris Sutton and Victor Sutton for technical assistance. We thank
Pathology Support Group, Cellular and Molecular Pathology Branch for
their help with histology. Orair1+/- (Cracm1+/-)
mice were provided by Dr. Jean-Pierre Kinet (Harvard Medical School). We
thank Dr. Carl Bortner, in the NIEHS Flow Cytometry Center for his help
in sorting and characterizing testicular cell populations. This research
was supported by the Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences.
NR 35
TC 0
Z9 0
U1 4
U2 5
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4160
EI 1532-1991
J9 CELL CALCIUM
JI Cell Calcium
PD APR
PY 2016
VL 59
IS 4
BP 189
EP 197
DI 10.1016/j.ceca.2016.02.007
PG 9
WC Cell Biology
SC Cell Biology
GA DL7GZ
UT WOS:000375810300006
PM 26969191
ER
PT J
AU Michaud, CR
Qin, J
Elkins, WR
Gozalo, AS
AF Michaud, Carmen R.
Qin, Jing
Elkins, William R.
Gozalo, Alfonso S.
TI Comparison of 3 Topical Treatments against Ulcerative Dermatitis in Mice
with a C57BL/6 Background
SO COMPARATIVE MEDICINE
LA English
DT Article
ID VITAMIN-E; HYPOCHLORITE; ASSOCIATION; VASCULITIS; INFECTION
AB Ulcerative dermatitis (UD) is a common condition in C57BL/6 mice and strains with this background. The etiology of UD is unclear but appears to have a genetic component associated with the C57BL/6 strain and has been reported as secondary to a variety of conditions. Treatment is unrewarding, resulting in euthanasia in many cases. In the present study we compared 3 topical treatments against spontaneous UD in mice with a C57BL/6 background. In total, 301 mice of both sexes were included in this study, and the tested treatments comprised bacitracin-neomycin sulfate-polymixin B sulfate ointment twice daily, 10% povidone-iodine ointment plus 1% silver sulfadiazine cream once daily, and 0.005% sodium hypochlorite once daily. Lesion healing was defined as complete skin reepithelialization with or without hair regrowth. Sex, age, lesion location, and type and length of treatment were analyzed by using univariate and multivariate logistic regression. Of the 79 mice treated with triple-antibiotic ointment, 27 (34%) healed, compared with 43 of the 125 (34%) treated with povidone-iodine and sulfadiazine and 69 of the 97 (71%) treated with hypochlorite. Lesion size and treatment with 0.005% sodium hypochlorite were the only significant predictors of healing; all other variables were not statistically significant in multivariate analysis. We conclude that 0.005% sodium hypochlorite is an effective topical treatment alternative for UD in C57BL/6 mice and strains on this background, and a favorable prognosis depends on the early identification and treatment of those lesions.
C1 [Michaud, Carmen R.; Elkins, William R.; Gozalo, Alfonso S.] NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Qin, Jing] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gozaloa@niaid.nih.gov
FU Intramural Research Program of the NIH, National Institute of Allergy
and Infectious Diseases, Comparative Medicine Branch
FX This study was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases, Comparative
Medicine Branch. We are very grateful to the investigators and technical
staff who made it possible for us to conduct this study.
NR 33
TC 1
Z9 1
U1 3
U2 4
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD APR
PY 2016
VL 66
IS 2
BP 100
EP 104
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA DL0VN
UT WOS:000375350800003
PM 27053563
ER
PT J
AU Updegrove, TB
Zhang, AX
Storz, G
AF Updegrove, Taylor B.
Zhang, Aixia
Storz, Gisela
TI Hfq: the flexible RNA matchmaker
SO CURRENT OPINION IN MICROBIOLOGY
LA English
DT Review
ID ESCHERICHIA-COLI HFQ; SM-LIKE PROTEIN; MESSENGER-RNA; SOLUBLE-RNAS;
BINDING PROPERTIES; RECOGNITION; CHAPERONE; COMPLEX; RPOS; TRANSLATION
AB The RNA chaperone protein Hfq is critical to the function of small, base pairing RNAs in many bacteria. In the past few years, structures and modeling of wild type Hfq and assays of various mutants have documented that the homohexameric Hfq ring can contact RNA at four sites (proximal face, distal face, rim and C-terminal tail) and that different RNAs bind to these sites in various configurations. These studies together with novel in vitro and in vivo experimental approaches are beginning to give mechanistic insights into how Hfq acts to promote small RNA-mRNA pairing and indicate that flexibility is integral to the Hfq role in RNA matchmaking.
C1 [Updegrove, Taylor B.; Zhang, Aixia; Storz, Gisela] NICHD, Div Mol & Cellular Biol, NIH, 18 Lib Dr MSC 5430, Bethesda, MD 20892 USA.
RP Storz, G (reprint author), NICHD, Div Mol & Cellular Biol, NIH, 18 Lib Dr MSC 5430, Bethesda, MD 20892 USA.
EM storzg@mail.nih.gov
OI Updegrove, Taylor/0000-0002-9763-3618
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [ZIA HD001608]
FX We thank S Gottesman and S Woodson and members of their groups for
comments. Work in the Storz laboratory is supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (Project ZIA HD001608).
NR 45
TC 10
Z9 10
U1 11
U2 22
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1369-5274
EI 1879-0364
J9 CURR OPIN MICROBIOL
JI Curr. Opin. Microbiol.
PD APR
PY 2016
VL 30
BP 133
EP 138
DI 10.1016/j.mib.2016.02.003
PG 6
WC Microbiology
SC Microbiology
GA DK2AI
UT WOS:000374716600018
PM 26907610
ER
PT J
AU Roederer, M
AF Roederer, Mario
TI Distributions of Autofluorescence After Compensation: Be Panglossian,
Fret Not
SO CYTOMETRY PART A
LA English
DT Article
DE instrumentation; controls; data analysis
AB In this technical note, I describe an in silico model of multiparameter fluorescence measurements that takes into account intrinsic cellular autofluorescence and stained dye fluorescence distributions, fluorescence spectrum spillovers, and photon counting statistics. Using this model, it is easy to manipulate spectral variables as well as error terms to understand the impact of each on the distributions of estimated cell-associated dyes (e.g., conjugated monoclonal antibodies in immunophenotyping). An application of this model was to understand the genesis of unusual autofluorescence distributions that occasionally happen in multi-color immunophenotyping. These unusual distributions show striking correlated patterns (diagonals) for graphs of certain pairs of parameters. Here I show that these arise from combinations of spillover-spreading from unviewed parameters. While disconcerting to researchers taught to look for diagonals in distributions as heralding improper compensation, these distributions are in fact appropriate. In general, one can ignore the characteristics of cell distributions within the same limits as background (e.g., as proscribed by a fluorescence-minus-one, or FMO, control), as there is essentially no information content in that region. Published 2016 International Society for Advancement of Cytometry.
C1 [Roederer, Mario] NIAID, Flow Cytometry Core, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Roederer, M (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA.
EM Roederer@nih.gov
FU Intramural Research Program of the Vaccine Research Center, NIAID, NIH
FX Grant sponsor: Intramural Research Program of the Vaccine Research
Center, NIAID, NIH.
NR 5
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD APR
PY 2016
VL 89A
IS 4
BP 398
EP 402
DI 10.1002/cyto.a.22820
PG 5
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DK2FQ
UT WOS:000374730400010
PM 26859757
ER
PT J
AU Darr, RW
Lenzner, S
Eggermann, T
Darr, WH
AF Daerr, Roland Wolfgang
Lenzner, Steffen
Eggermann, Thomas
Daerr, Wolfgang Hermann
TI Xanthinuria Type 1 in a Patient with Joint Pains
SO DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
LA German
DT Article
ID ACUTE-RENAL-FAILURE; INBORN-ERRORS; HEREDITARY XANTHINURIA; CLASSICAL
XANTHINURIA; HYPOURICEMIA; MUTATIONS; EXERCISE; DEFICIENCY; METABOLISM;
GENE
C1 [Daerr, Roland Wolfgang] NICHD, Innere Med Diabetol & Endokrinol, Zeit Stipendiat Deutsch Forschungsgemeinsch, NIH,Bereich Neuroendokrinol, Bethesda, MD USA.
[Lenzner, Steffen] Inst Med Diagnost GmbH, Abteilungsleiter Teilbereich Mol Genet, Ingelheim, Germany.
[Eggermann, Thomas] Inst Humangenet RWTH, Aachen, Germany.
[Daerr, Wolfgang Hermann] Vivantes Klinikum Friedrichshain, Klin Innere Med Nephrol, Berlin, Germany.
[Daerr, Wolfgang Hermann] Klinikum Dobeln, Dobeln, Germany.
RP Darr, RW (reprint author), NICHD, Innere Med Diabetol & Endokrinol, Zeit Stipendiat Deutsch Forschungsgemeinsch, NIH,Bereich Neuroendokrinol, Bethesda, MD USA.; Lenzner, S (reprint author), Inst Med Diagnost GmbH, Abteilungsleiter Teilbereich Mol Genet, Ingelheim, Germany.; Eggermann, T (reprint author), Inst Humangenet RWTH, Aachen, Germany.; Darr, WH (reprint author), Vivantes Klinikum Friedrichshain, Klin Innere Med Nephrol, Berlin, Germany.; Darr, WH (reprint author), Klinikum Dobeln, Dobeln, Germany.
EM roland_daerr@web.de; steffen.lenzner@bioscientia.de;
teggermann@ukaachen.de; wolfgang-daerr@t-online.de
NR 35
TC 0
Z9 0
U1 1
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0012-0472
EI 1439-4413
J9 DEUT MED WOCHENSCHR
JI Dtsch. Med. Wochenschr.
PD APR
PY 2016
VL 141
IS 8
BP 571
EP +
DI 10.1055/s-0041-106053
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DJ8XC
UT WOS:000374496200022
PM 27078247
ER
PT J
AU Levenson, AE
Haas, ME
Miao, J
Brown, RJ
de Ferranti, SD
Muniyappa, R
Biddinger, SB
AF Levenson, Amy E.
Haas, Mary E.
Miao, Ji
Brown, Rebecca J.
de Ferranti, Sarah D.
Muniyappa, Ranganath
Biddinger, Sudha B.
TI Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female
Lipodystrophic Patients
SO ENDOCRINOLOGY
LA English
DT Article
ID DENSITY-LIPOPROTEIN RECEPTOR; LONG-TERM EFFICACY; LDL CHOLESTEROL;
PLASMA PCSK9; GENERALIZED LIPODYSTROPHY; INSULIN-RESISTANCE; OBESE MICE;
PROTEIN; HYPERCHOLESTEROLEMIA; METABOLISM
AB Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (similar to 24 mu g/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (similar to 4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 +/- 109 vs 221 +/- 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.
C1 [Levenson, Amy E.; Haas, Mary E.; Miao, Ji; Biddinger, Sudha B.] Harvard Univ, Sch Med, Div Endocrinol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Brown, Rebecca J.; Muniyappa, Ranganath] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[de Ferranti, Sarah D.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA 02115 USA.
RP Biddinger, SB (reprint author), Boston Childrens Hosp, CLSB 16027,300 Longwood Ave, Boston, MA 02115 USA.
EM sudha.biddinger@childrens.harvard.edu
OI Haas, Mary Elizabeth/0000-0002-2816-9268
FU National Institutes of Health [R01HL109650-05, 5K12DK094721-05,
K99DK100539-02]; Department of Defense through the National Defense
Science and Engineering Graduate Fellowship Program; Farb Family Fund;
Kostin Family Innovation Fund; Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by National Institutes of Health Grants
R01HL109650-05 (to S.B.B.), 5K12DK094721-05 (to A.E.L.), and
K99DK100539-02 to (J.M.); M.E.H. was supported by the Department of
Defense through the National Defense Science and Engineering Graduate
Fellowship Program; S.D.d.F. was supported by the Farb Family Fund and
by the Kostin Family Innovation Fund. Human studies were funded by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 52
TC 0
Z9 0
U1 2
U2 4
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD APR
PY 2016
VL 157
IS 4
BP 1421
EP 1429
DI 10.1210/en.2015-1624
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK0CK
UT WOS:000374579800013
PM 26824363
ER
PT J
AU Zemkova, H
Tomic, M
Kucka, M
Aguilera, G
Stojilkovic, SS
AF Zemkova, Hana
Tomic, Melanija
Kucka, Marek
Aguilera, Greti
Stojilkovic, Stanko S.
TI Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice
Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels
SO ENDOCRINOLOGY
LA English
DT Article
ID HYPOPHYSEAL PORTAL BLOOD; ANTERIOR-PITUITARY-CELLS; SECRETING ADENOMA
CELLS; PROTEIN-KINASE-A; K+ BK CHANNELS; ARGININE-VASOPRESSIN; RAT
CORTICOTROPES; CA2+ ENTRY; ELECTRICAL-ACTIVITY; ARACHIDONIC-ACID
AB Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling.
C1 [Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Videnska 1083, CR-14220 Prague 4, Czech Republic.
[Zemkova, Hana; Tomic, Melanija; Kucka, Marek; Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA.
[Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA.
RP Zemkova, H (reprint author), Acad Sci Czech Republic, Inst Physiol, Videnska 1083, CR-14220 Prague 4, Czech Republic.
EM zemkova@biomed.cas.cz
RI Zemkova, Hana/C-1844-2012
FU Grant Agency of the Czech Republic [P304/12/G069]; Ministry of
Education, Youth and Sports of CR within National Sustainability Program
II (Project BIOCEV-FAR) [LQ1604]; project "BIOCEV"
[CZ.1.05/1.1.00/02.0109]; Intramural Research Program of the National
Institute of Child Health and Human Development, National Institute of
Health
FX This work was supported by the Grant Agency of the Czech Republic
P304/12/G069, the Ministry of Education, Youth and Sports of CR within
the LQ1604 National Sustainability Program II (Project BIOCEV-FAR) and
by the project "BIOCEV" (CZ.1.05/1.1.00/02.0109) (to H.Z.), and by a
grant from the Intramural Research Program of the National Institute of
Child Health and Human Development, National Institute of Health (M.T.,
M.K., G.A., and S.S.S.).
NR 46
TC 1
Z9 1
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD APR
PY 2016
VL 157
IS 4
BP 1576
EP 1589
DI 10.1210/en.2015-1899
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK0CK
UT WOS:000374579800026
PM 26901094
ER
PT J
AU Charmoy, M
Hurrell, BP
Romano, A
Lee, SH
Ribeiro-Gomes, F
Riteau, N
Mayer-Barber, K
Tacchini-Cottier, F
Sacks, DL
AF Charmoy, Melanie
Hurrell, Benjamin P.
Romano, Audrey
Lee, Sang Hun
Ribeiro-Gomes, Flavia
Riteau, Nicolas
Mayer-Barber, Katrin
Tacchini-Cottier, Fabienne
Sacks, David L.
TI The Nlrp3 inflammasome, IL-1 beta, and neutrophil recruitment are
required for susceptibility to a nonhealing strain of Leishmania major
in C57BL/6 mice
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE IL-1 beta; Leishmaniasis; Nlrp3 inflammasome; Neutrophils; Skin
ID CUTANEOUS LEISHMANIASIS; IMMUNE-RESPONSE; NATURAL MODEL; CXCR2 LIGAND;
KC/GRO-ALPHA; INFECTION; DEFICIENT; CELLS; RESISTANCE; APOPTOSIS
AB Infection of C57BL/6 mice with most Leishmania major strains results in a healing lesion and clearance of parasites from the skin. Infection of C57BL/6 mice with the L. major Seidman strain (LmSd), isolated from a patient with chronic lesions, despite eliciting a strong Th1 response, results in a nonhealing lesion, poor parasite clearance, and complete destruction of the ear dermis. We show here that in comparison to a healing strain, LmSd elicited early upregulation of IL-1 beta mRNA and IL-1 beta-producing dermal cells and prominent neutrophil recruitment to the infected skin. Mice deficient in Nlrp3, apoptosis-associated speck-like protein containing a caspase recruitment domain, or caspase-1/11, or lacking IL-1 beta or IL-1 receptor signaling, developed healing lesions and cleared LmSd from the infection site. Mice resistant to LmSd had a stronger antigen-specific Th1 response. The possibility that IL-1 beta might act through neutrophil recruitment to locally suppress immunity was supported by the healing observed in neutropenic Genista mice. Secretion of mature IL-1 beta by LmSd-infected macrophages in vitro was dependent on activation of the Nlrp3 inflammasome and caspase-1. These data reveal that Nlrp3 inflammasome-dependent IL-1 beta, associated with localized neutrophil recruitment, plays a crucial role in the development of a nonhealing form of cutaneous leishmaniasis in conventionally resistant mice.
C1 [Charmoy, Melanie; Romano, Audrey; Lee, Sang Hun; Ribeiro-Gomes, Flavia; Riteau, Nicolas; Mayer-Barber, Katrin; Sacks, David L.] NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm B1-12,Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
[Hurrell, Benjamin P.; Tacchini-Cottier, Fabienne] Univ Lausanne, Dept Biochem, WHO Immunol Res & Training Ctr, Lausanne, Switzerland.
RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm B1-12,Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Swiss National
Foundation [310030.146187/1]
FX We thank Kim Beacht for assistance with the animal infection studies,
and Dragana Jankovic for helpful discussions and provision of the
IL-27Ra-/- mice, and Marie and Bernard Malissen for the
Genista mice. This work was supported in part by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, and in part by the Swiss National
Foundation, grant 310030.146187/1 to F.T.C.
NR 41
TC 6
Z9 6
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD APR
PY 2016
VL 46
IS 4
BP 897
EP 911
DI 10.1002/eji.201546015
PG 15
WC Immunology
SC Immunology
GA DJ9SH
UT WOS:000374552700012
PM 26689285
ER
PT J
AU Cabrera, SM
Wang, XJ
Chen, YG
Jia, S
Kaldunski, ML
Greenbaum, CJ
Mandrup-Poulsen, T
Hessner, MJ
AF Cabrera, Susanne M.
Wang, Xujing
Chen, Yi-Guang
Jia, Shuang
Kaldunski, Mary L.
Greenbaum, Carla J.
Mandrup-Poulsen, Thomas
Hessner, Martin J.
CA Type 1 Diabet TrialNet Canakinumab
AIDA Study Grp
TI Interleukin-1 antagonism moderates the inflammatory state associated
with Type 1 diabetes during clinical trials conducted at disease onset
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Anakinra; Canakinumab; Interleukin-1; Transcriptional signatures; Type 1
diabetes
ID RAT PANCREATIC-ISLETS; MELLITUS; SERUM; EXPRESSION; MOUSE;
BIOINFORMATICS; IDENTIFICATION; BIOSYNTHESIS; LANGERHANS; IL-1-ALPHA
AB It was hypothesized that IL-1 antagonism would preserve beta-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1 alpha and IL-1 beta additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials.
C1 [Cabrera, Susanne M.; Chen, Yi-Guang; Jia, Shuang; Kaldunski, Mary L.; Hessner, Martin J.] Childrens Hosp Wisconsin, Max McGee Natl Res Ctr Juvenile Diabet, Childrens Res Inst, Milwaukee, WI 53201 USA.
[Cabrera, Susanne M.; Chen, Yi-Guang; Jia, Shuang; Kaldunski, Mary L.; Hessner, Martin J.; Type 1 Diabet TrialNet Canakinumab; AIDA Study Grp] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Wang, Xujing] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Greenbaum, Carla J.] Benaroya Res Inst, Diabet Res Program, Seattle, WA USA.
[Mandrup-Poulsen, Thomas] Univ Copenhagen, Dept Biomed Sci, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Mandrup-Poulsen, Thomas] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
RP Hessner, MJ (reprint author), Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
EM mhessner@mcw.edu
OI Castano, Luis/0000-0003-0437-9401
FU Juvenile Diabetes Research Foundation [1-2008-1026, 5-2012-220,
17-2012-621, 2-SRA-2015-109-Q-R]; American Diabetes Association
[7-12-BS-075]; National Institutes of Health [R01AI078713, DP3DK098161,
R01DK080100]; National Center for Advancing Translational Sciences,
National Institutes of Health [8UL1TR000055]; Children's Hospital of
Wisconsin Foundation; National Institutes of Health through the National
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver
National Institute of Child Health and Human Development [U01 DK061010,
U01 DK061016, U01 DK061034, U01 DK061036, U01 DK061040, U01 DK061041,
U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453,
U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085505,
U01 DK085509, HHSN267200800019C]; National Center for Research
Resources, through Clinical Translational Science Awards [UL1 RR024131,
UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744,
UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986]; General
Clinical Research Center Award [M01 RR00400]; JDRF; American Diabetes
Association; Type 1 Diabetes TrialNet Study Group
FX This ancillary study was supported by The Juvenile Diabetes Research
Foundation International (grants 1-2008-1026, 5-2012-220, 17-2012-621,
2-SRA-2015-109-Q-R to M.J.H.); American Diabetes Association (grant
7-12-BS-075 to M.J.H.); National Institutes of Health (grants
R01AI078713 to M.J.H., DP3DK098161 to M.J.H./C.J.G., R01DK080100 to
X.W., and the National Center for Advancing Translational Sciences,
National Institutes of Health grant 8UL1TR000055); and The Children's
Hospital of Wisconsin Foundation.; The canakinumab trial was sponsored
by the Type 1 Diabetes TrialNet Study Group. The Type 1 Diabetes
TrialNet Study Group is a clinical trials network funded by the National
Institutes of Health through the National Institute of Diabetes and
Digestive and Kidney Diseases, the National Institute of Allergy and
Infectious Diseases, and The Eunice Kennedy Shriver National Institute
of Child Health and Human Development, through the cooperative
agreements U01 DK061010, U01 DK061016, U01 DK061034, U01 DK061036, U01
DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01
DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01
DK085499, U01 DK085505, U01 DK085509, and contract HHSN267200800019C;
the National Center for Research Resources, through Clinical
Translational Science Awards UL1 RR024131, UL1 RR024139, UL1 RR024153,
UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780,
UL1 RR029890, UL1 RR031986, and General Clinical Research Center Award
M01 RR00400; the JDRF; and the American Diabetes Association. Novartis
(Basel, Switzerland) provided canakinumab (Ilaris), input regarding
dosage, and other suggestions but had no direct involvement with study
design, conduct, or management; data collection, analysis or
interpretation; or manuscript preparation. Roche Diagnostics provided
blood glucose monitoring meters and strips to research participants in
the canakinumab trial.
NR 38
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD APR
PY 2016
VL 46
IS 4
BP 1030
EP 1046
DI 10.1002/eji.201546005
PG 17
WC Immunology
SC Immunology
GA DJ9SH
UT WOS:000374552700025
PM 26692253
ER
PT J
AU Fansiri, T
Pongsiri, A
Klungthong, C
Ponlawat, A
Thaisomboonsuk, B
Jarman, RG
Scott, TW
Lambrechts, L
AF Fansiri, Thanyalak
Pongsiri, Arissara
Klungthong, Chonticha
Ponlawat, Alongkot
Thaisomboonsuk, Butsaya
Jarman, Richard G.
Scott, Thomas W.
Lambrechts, Louis
TI No evidence for local adaptation of dengue viruses to mosquito vector
populations in Thailand
SO EVOLUTIONARY APPLICATIONS
LA English
DT Article
DE Aedes aegypti; dengue virus; genotype x genotype interactions; local
adaptation; population structure
ID AEDES-AEGYPTI POPULATIONS; KAMPHAENG-PHET; ORAL-SUSCEPTIBILITY; GLOBAL
DISTRIBUTION; CLADE REPLACEMENT; GENETIC-STRUCTURE; TRANSMISSION;
INFECTION; STRAINS; MEXICO
AB Despite their epidemiological importance, the evolutionary forces that shape the spatial structure of dengue virus genetic diversity are not fully understood. Fine-scale genetic structure of mosquito vector populations and evidence for genotype x genotype interactions between dengue viruses and their mosquito vectors are consistent with the hypothesis that the geographical distribution of dengue virus genetic diversity may reflect viral adaptation to local mosquito populations. To test this hypothesis, we measured vector competence in all sympatric and allopatric combinations of 14 low-passage dengue virus isolates and two wild-type populations of Aedes aegypti mosquitoes sampled in Bangkok and Kamphaeng Phet, two sites located about 300km apart in Thailand. Despite significant genotype x genotype interactions, we found no evidence for superior vector competence in sympatric versus allopatric vector-virus combinations. Viral phylogenetic analysis revealed no geographical clustering of the 14 isolates, suggesting that high levels of viral migration (gene flow) in Thailand may counteract spatially heterogeneous natural selection. We conclude that it is unlikely that vector-mediated selection is a major driver of dengue virus adaptive evolution at the regional scale that we examined. Dengue virus local adaptation to mosquito vector populations could happen, however, in places or times that we did not test, or at a different geographical scale.
C1 [Fansiri, Thanyalak; Pongsiri, Arissara; Ponlawat, Alongkot] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand.
[Klungthong, Chonticha; Thaisomboonsuk, Butsaya; Jarman, Richard G.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Lambrechts, Louis] Inst Pasteur, Dept Genomes & Genet, Insect Virus Interact Grp, 28 Rue Docteur Roux, F-75724 Paris 15, France.
[Lambrechts, Louis] Ctr Natl Rech Sci, Unite Rech Associee, Paris, France.
[Jarman, Richard G.] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MD USA.
RP Lambrechts, L (reprint author), Inst Pasteur, Dept Genomes & Genet, Insect Virus Interact Grp, 28 Rue Docteur Roux, F-75724 Paris 15, France.
EM louis.lambrechts@pasteur.fr
RI Lambrechts, Louis/A-2057-2010
OI Lambrechts, Louis/0000-0001-5958-2138
FU United States National Institutes of Health [R01-GM083224]; United
States Military Infectious Diseases Research Program; French Agence
Nationale de la Recherche [ANR-09-RPDOC-007-01]; French Government's
Investissement d'Avenir program, Laboratoire d'Excellence Integrative
Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]; City of
Paris Emergence(s) program in Biomedical Research; Research and Policy
for Infectious Disease Dynamics program of the Science and Technology
Directorate, Department of Homeland Security; Fogarty International
Center, United States National Institutes of Health; United States
National Institutes of Health and Human Services [P01-AI098670]
FX We acknowledge the invaluable contributions of the clinical, laboratory,
and entomological personnel of AFRIMS and Kamphaeng Phet AFRIMS Virology
Research Unit (KAVRU). We are grateful to Robert Gibbons, Stefan
Fernandez, Timothy Endy, Anthony Schuster, and three anonymous reviewers
for their insights. The opinions or assertions contained herein are the
private views of the authors and are not to be construed as reflecting
the official views of the United States Army, Royal Thai Army, or the
United States Department of Defense. This study was primarily supported
by grant R01-GM083224 from the United States National Institutes of
Health and by the United States Military Infectious Diseases Research
Program. L.L. received funding from the French Agence Nationale de la
Recherche (grant ANR-09-RPDOC-007-01), the French Government's
Investissement d'Avenir program, Laboratoire d'Excellence Integrative
Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID),
and the City of Paris Emergence(s) program in Biomedical Research.
T.W.S. received support from the Research and Policy for Infectious
Disease Dynamics program of the Science and Technology Directorate,
Department of Homeland Security, and Fogarty International Center,
United States National Institutes of Health. L.L. and T.W.S. received
support from the United States National Institutes of Health and Human
Services (grant P01-AI098670). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 47
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-4571
J9 EVOL APPL
JI Evol. Appl.
PD APR
PY 2016
VL 9
IS 4
BP 608
EP 618
DI 10.1111/eva.12360
PG 11
WC Evolutionary Biology
SC Evolutionary Biology
GA DJ9SM
UT WOS:000374553200007
PM 27099625
ER
PT J
AU Thorgeirsson, SS
AF Thorgeirsson, Snorri S.
TI Stemness and Reprogramming in Liver Cancer
SO HEPATOLOGY
LA English
DT Editorial Material
ID BILIARY ORIGIN; CELL ORIGIN; HEPATOCYTES
C1 [Thorgeirsson, Snorri S.] NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NIH, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,MSC 4262,Bldg 37,Room 4128B, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
NR 20
TC 0
Z9 0
U1 4
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD APR
PY 2016
VL 63
IS 4
BP 1068
EP 1070
DI 10.1002/hep.28362
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DK2HW
UT WOS:000374736300001
PM 26600290
ER
PT J
AU Unalp-Arida, A
Ruhl, CE
AF Unalp-Arida, Aynur
Ruhl, Constance E.
TI Noninvasive Fatty Liver Markers Predict Liver Disease Mortality in the
US Population
SO HEPATOLOGY
LA English
DT Article
ID SERUM ALANINE AMINOTRANSFERASE; NUTRITION EXAMINATION SURVEY;
UNITED-STATES POPULATION; SUPERFAMILY MEMBER 2; 3RD NATIONAL-HEALTH;
CARDIOVASCULAR-DISEASE; NONALCOHOLIC STEATOHEPATITIS; CONFERS
SUSCEPTIBILITY; CAFFEINE CONSUMPTION; HEPATIC STEATOSIS
AB Nonalcoholic fatty liver disease (NAFLD) contributes to premature death along with obesity, diabetes, and cardiovascular disease (CVD). We examined whether hepatic steatosis (HS) on ultrasound and liver enzyme activities were associated with increased liver disease mortality in the U.S. National Health and Nutrition Examination Survey (NHANES), 1988-1994, with up to 23 years of linked-mortality data. Survey-linked National Death Index records were analyzed among 14,527 adult participants who were negative for viral hepatitis B and C and iron overload. HS on ultrasound was categorized as normal, mild, moderate, or severe. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) elevation was defined as the highest sex-specific decile. Cumulative mortality was 36.2% from all causes, including 16.3% from CVD, 10.8% from cancer, 5.4% from diabetes, and 1.1% from liver disease. Severe HS was associated with increased liver disease mortality in both age-adjusted (hazard ratio [HR]: 3.92; 95% confidence interval [CI]: 1.49-10.27; P for trend: 0.011) and multivariate-adjusted analyses (HR, 2.68; 95% CI: 1.02-7.03; P for trend: 0.072). HS was not independently associated with mortality from all causes, CVD, cancer, or diabetes. Higher liver disease mortality was found with elevated ALT (HR, 4.08; 95% CI: 1.99-8.33), AST (HR, 4.33; 95% CI: 2.18-8.59), and GGT (HR, 7.91; 95% CI: 3.06-20.46). GGT elevation was associated with increased overall mortality (HR, 1.45; 95% CI: 1.21-1.74). Liver enzymes were otherwise unrelated to overall or cause-specific mortality. Conclusions: In the U. S. population, severe hepatic steatosis on ultrasound and liver enzyme elevation were associated with increased liver disease mortality, but were not independently associated with mortality from all causes (except for GGT), CVD, cancer, or diabetes.
C1 [Unalp-Arida, Aynur] NIDDK, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Ruhl, Constance E.] Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM cruhl@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN276201200161U]
FX The work was supported by a contract from the National Institute of
Diabetes and Digestive and Kidney Diseases (HHSN276201200161U).
NR 47
TC 2
Z9 2
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD APR
PY 2016
VL 63
IS 4
BP 1170
EP 1183
DI 10.1002/hep.28390
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DK2HW
UT WOS:000374736300015
PM 26663021
ER
PT J
AU Chrysostomou, PP
Lodish, MB
Turkbey, EB
Papadakis, GZ
Stratakis, CA
AF Chrysostomou, P. P.
Lodish, M. B.
Turkbey, E. B.
Papadakis, G. Z.
Stratakis, C. A.
TI Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in
Patients with Primary Pigmented Nodular Adrenocortical Disease
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE PPNAD; 3D imaging; CT; adrenals; cushing's syndrome
ID CUSHINGS-SYNDROME; COMPUTED-TOMOGRAPHY; PRKAR1A GENE; DIAGNOSIS; TUMORS;
DEXAMETHASONE; HYPERPLASIAS; MUTATIONS; COMPLEX
AB Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing's syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8 +/- 17.6 years) and 8 controls (19 +/- 3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc +/- 4.1, 7.2 cc +/- 4.5 (p=0.643) for non-CS, and 8.0cc +/- 1.6 for controls. Mean values were corrected for body surface area; 4.7cc/kg/m(2)+/- 2.2 for CS, and 3.9cc/kg/m(2)+/- 1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do.
C1 [Chrysostomou, P. P.; Lodish, M. B.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Turkbey, E. B.] NIH, Ctr Clin, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
[Turkbey, E. B.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Papadakis, G. Z.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NIH, Div Intramural Res, 31 Ctr Dr Bldg 31 Room 2A46 MSC 2425, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU NICHO, NIH
FX This work was supported by the Intramural Research Program, NICHO, NIH.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
EI 1439-4286
J9 HORM METAB RES
JI Horm. Metab. Res.
PD APR
PY 2016
VL 48
IS 4
BP 242
EP 246
DI 10.1055/s-0042-103686
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DJ5JF
UT WOS:000374242700005
PM 27065461
ER
PT J
AU Osinga, TE
Xekouki, P
Nambuba, J
Faucz, FR
Sierra, MD
Links, TP
Kema, IP
Adams, K
Stratakis, CA
van der Horst-Schrivers, ANA
Pacak, K
AF Osinga, T. E.
Xekouki, P.
Nambuba, J.
Faucz, F. R.
Sierra, M. de la Luz
Links, T. P.
Kema, I. P.
Adams, K.
Stratakis, C. A.
van der Horst-Schrivers, A. N. A.
Pacak, K.
TI SDH Subunit Mutation Status in Saliva: Genetic Testing in Patients with
Pheochromocytoma
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE SDHx mutations; pheochromocytoma; paraganglioma; DNA; saliva
ID PARAGANGLIOMA
AB Germline mutations occur in up to 30-40% of pheochromocytoma/paraganglioma, with mutations in the succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD) being the most common. Blood samples are favored for obtaining high quality DNA, however, leukocytes can also be obtained by collecting saliva. The aim of this study was to determine whether SDHB and SDHD gene mutations in patients with pheochromocytoma/paraganglioma could be determined using a salivary sample. Paired blood and salivary samples were collected from 30 patients: 9 SDHB mutation positive, 13 with a SDHD mutation, and 8 without any SDHx mutations. The Oragene DISCOVER kit was used to collect and extract DNA from saliva. Blood DNA was extracted from EDTA blood samples. The DNA purification and concentration were measured by spectrophotometry. The 8 exons of SDHB and the 4 exons of SDHD were amplified and sequenced by PCR-based bidirectional Sanger sequencing. Total DNA yields from blood DNA were similar to those obtained from saliva DNA [mean (+/- SD) saliva vs. blood DNA concentration 514.6 (+/- 580.8)ng/mu l vs. 360.9 (+/- 262.7)ng/mu l; p=0.2)]. The purity of the saliva DNA samples was lower than that of blood [mean OD260/OD280 ratio 1.78 (+/- 0.13) vs. 1.87 (+/- 0.04); p=0.001, respectively], indicating more protein contamination in the saliva-extracted DNA. This study shows that salivary DNA collected from patients with pheochromocytoma/paraganglioma is a good alternative for extraction of genomic DNA for its high DNA concentration and acceptable purity and can be used as an alternative to blood derived DNA in screening for SDHB and SDHD mutations.
C1 [Osinga, T. E.; Nambuba, J.; Adams, K.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Osinga, T. E.; Links, T. P.; van der Horst-Schrivers, A. N. A.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol & Metab Dis, Groningen, Netherlands.
[Xekouki, P.; Faucz, F. R.; Sierra, M. de la Luz; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Kema, I. P.] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands.
RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Med, NIH, Bldg 10,CRC,Room 1E-3140 10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX This work was supported, in part, by the Intramural Research Program of
the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD).
NR 9
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
EI 1439-4286
J9 HORM METAB RES
JI Horm. Metab. Res.
PD APR
PY 2016
VL 48
IS 4
BP 247
EP 250
DI 10.1055/s-0035-1569265
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DJ5JF
UT WOS:000374242700006
PM 26916530
ER
PT J
AU Vinnakota, KC
Cha, CY
Rorsman, P
Balaban, RS
La Gerche, A
Wade-Martins, R
Beard, DA
Jeneson, JAL
AF Vinnakota, Kalyan C.
Cha, Chae Y.
Rorsman, Patrik
Balaban, Robert S.
La Gerche, Andre
Wade-Martins, Richard
Beard, Daniel A.
Jeneson, Jeroen A. L.
TI Improving the physiological realism of experimental models
SO INTERFACE FOCUS
LA English
DT Review
DE physiology; experimental models; human
ID PANCREATIC BETA-CELLS; RAT-HEART MITOCHONDRIA; WORKING RABBIT HEART;
PLURIPOTENT STEM-CELLS; OXIDATIVE-PHOSPHORYLATION; SKELETAL-MUSCLE;
PARKINSONS-DISEASE; INSULIN-SECRETION; CALCIUM UNIPORTER; MYOCARDIAL
OXYGENATION
AB The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.
C1 [Vinnakota, Kalyan C.; Beard, Daniel A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Cha, Chae Y.; Rorsman, Patrik] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford OX3 7LJ, England.
[Balaban, Robert S.] NHLBI, Lab Cardiac Energet, Bldg 10, Bethesda, MD 20892 USA.
[La Gerche, Andre] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Wade-Martins, Richard] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford, England.
[Wade-Martins, Richard] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
[Jeneson, Jeroen A. L.] Univ Groningen, Univ Med Ctr Groningen, Div Neurosci, Neuroimaging Ctr, NL-9713 AV Groningen, Netherlands.
[Jeneson, Jeroen A. L.] Univ Amsterdam, Acad Med Ctr Amsterdam, Dept Radiol, Amsterdam, Netherlands.
RP Jeneson, JAL (reprint author), Univ Groningen, Univ Med Ctr Groningen, Div Neurosci, Neuroimaging Ctr, NL-9713 AV Groningen, Netherlands.
EM j.a.l.jeneson@umcg.nl
OI Vinnakota, Kalyan/0000-0003-2185-2213
FU NIH [HL072011, GM094503]; Wellcome Trust
FX This work was supported in part by NIH grants HL072011 (JALJ and DAB)
and GM094503 (DAB) and by a Wellcome Trust senior investigator award
(PR).
NR 112
TC 1
Z9 1
U1 1
U2 4
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2042-8898
EI 2042-8901
J9 INTERFACE FOCUS
JI Interface Focus
PD APR
PY 2016
VL 6
IS 2
AR 20150076
DI 10.1098/rsfs.2015.0076
PG 14
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DL1RY
UT WOS:000375410900002
PM 27051507
ER
PT J
AU Agbor-Enoh, S
Doveikis, J
Zhu, J
Tunc, I
Wang, X
Jackson, A
Solomon, M
Valentine, H
AF Agbor-Enoh, S.
Doveikis, J.
Zhu, J.
Tunc, I.
Wang, X.
Jackson, A.
Solomon, M.
Valentine, H.
TI Urine Cell-Free Donor-Derived DNA (ucfdDNA) after Heart Transplantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Agbor-Enoh, S.; Doveikis, J.; Zhu, J.; Tunc, I.; Wang, X.; Solomon, M.; Valentine, H.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Jackson, A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 20
BP S16
EP S16
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718100021
ER
PT J
AU Chan, JL
Singh, AK
Thomas, ML
Ayares, DL
Horvath, KA
Mohiuddin, MM
AF Chan, J. L.
Singh, A. K.
Thomas, M. L.
Ayares, D. L.
Horvath, K. A.
Mohiuddin, M. M.
TI Multi-Transgenic Expression for Improved Xenograft Survival in
Pig-to-Baboon Heart Xenotransplantation Model
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Chan, J. L.; Singh, A. K.; Horvath, K. A.; Mohiuddin, M. M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Thomas, M. L.] NIH, Div Vet Resources, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA.
[Ayares, D. L.] Revivicor Inc, Blacksburg, VA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 104
BP S47
EP S48
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718100105
ER
PT J
AU Danziger-Isakov, L
Buller, R
Williams, N
Mason, S
Fenchel, M
Astor, T
Conrad, C
Faro, A
Goldfarb, S
Hayes, D
Melicoff-Portillo, E
Schecter, M
Visner, G
Ikle, D
Storch, G
Sweet, S
AF Danziger-Isakov, L.
Buller, R.
Williams, N.
Mason, S.
Fenchel, M.
Astor, T.
Conrad, C.
Faro, A.
Goldfarb, S.
Hayes, D.
Melicoff-Portillo, E.
Schecter, M.
Visner, G.
Ikle, D.
Storch, G.
Sweet, S.
TI Respiratory Viral Infections Are Common in the First Year After
Pediatric Lung Transplantation: A Multi-Center Prospective Study
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Danziger-Isakov, L.; Fenchel, M.; Schecter, M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Buller, R.; Mason, S.; Faro, A.; Storch, G.; Sweet, S.] Washington Univ, St Louis, MO USA.
[Williams, N.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Astor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Conrad, C.] Lucille Packard Childrens Hosp, Palo Alto, CA USA.
[Goldfarb, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Hayes, D.] Nationwide Childrens Hosp, Columbus, OH USA.
[Melicoff-Portillo, E.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Visner, G.] Boston Childrens Hosp, Boston, MA USA.
[Ikle, D.] Rho Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 71
BP S35
EP S35
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718100072
ER
PT J
AU Evans, CF
Sanchez, PG
Kon, ZN
Wang, X
Valantine, H
Agbor-Enoh, S
Iacono, AT
Griffith, BP
Pham, SM
AF Evans, C. F.
Sanchez, P. G.
Kon, Z. N.
Wang, X.
Valantine, H.
Agbor-Enoh, S.
Iacono, A. T.
Griffith, B. P.
Pham, S. M.
TI The Association between Donor-Recipient Race Matching and Survival
Following Lung Transplantation Differs Based on Recipient Race
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Evans, C. F.; Sanchez, P. G.; Kon, Z. N.; Wang, X.; Griffith, B. P.; Pham, S. M.] Univ Maryland, Sch Med, Surg, Baltimore, MD 21201 USA.
[Valantine, H.; Agbor-Enoh, S.] NHLBI, Genom Res Alliance Organ Transplantat, Baltimore, MD USA.
[Iacono, A. T.] R Adams Cowley Shock Trauma Ctr, Pulm & Transplant Med, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 1036
BP S371
EP S371
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718101386
ER
PT J
AU Parrish, A
Fenchel, M
Storch, G
Bulle, R
Mason, S
Mason, S
Williams, N
Ikle, D
Sweet, S
Danziger-Isakov, L
AF Parrish, A.
Fenchel, M.
Storch, G.
Bulle, R.
Mason, S.
Mason, S.
Williams, N.
Ikle, D.
Sweet, S.
Danziger-Isakov, L.
TI Evaluation of Epstein-Barr Viral Loads as a Predictor of Development of
Post-Transplant Lymphoproliferative Disorder
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Parrish, A.; Fenchel, M.; Danziger-Isakov, L.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Storch, G.; Bulle, R.; Mason, S.; Mason, S.; Sweet, S.] Washington Univ, St Louis, MO USA.
[Williams, N.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ikle, D.] Rho Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 969
BP S349
EP S349
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718101324
ER
PT J
AU Siddiqui, AH
Weir, NA
WoldeHanna, ML
Mazer, AJ
Biancotto, A
Cai, R
Grariingen, G
Harper, B
Sun, J
Nathan, SD
Danner, RL
Solomon, MA
Elinoff, JM
AF Siddiqui, A. H.
Weir, N. A.
WoldeHanna, M. Lemma
Mazer, A. J.
Biancotto, A.
Cai, R.
Grariingen, G.
Harper, B.
Sun, J.
Nathan, S. D.
Danner, R. L.
Solomon, M. A.
Elinoff, J. M.
TI Serum Cytokine Profiling in Pulmonary Arterial Hypertension
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation (ISHLT)
CY APR 27-30, 2016
CL Washington, DC
SP Int Soc Heart & Lung Transplantat
C1 [Siddiqui, A. H.; Mazer, A. J.; Cai, R.; Grariingen, G.; Harper, B.; Sun, J.; Danner, R. L.; Elinoff, J. M.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Weir, N. A.; WoldeHanna, M. Lemma; Nathan, S. D.] Inova Fainfax Hosp, Inova Adv Lung Dis & Transplant Program, Falls Church, VA USA.
[Biancotto, A.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bldg 10, Bethesda, MD 20892 USA.
[Solomon, M. A.] NHLBI, Dept Crit Care Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Solomon, M. A.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2016
VL 35
IS 4
SU S
MA 1003
BP S360
EP S360
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA DK2AX
UT WOS:000374718101354
ER
PT J
AU Bowsher, K
Civillico, EF
Coburn, J
Collinger, J
Contreras-Vidal, JL
Denison, T
Donoghue, J
French, J
Getzoff, N
Hochberg, LR
Hoffmann, M
Judy, J
Kleitman, N
Knaack, G
Krauthamer, V
Ludwig, K
Moynahan, M
Pancrazio, JJ
Peckham, PH
Pena, C
Pinto, V
Ryan, T
Saha, D
Scharen, H
Shermer, S
Skodacek, K
Takmakov, P
Tyler, D
Vasudevan, S
Wachrathit, K
Weber, D
Welle, CG
Ye, M
AF Bowsher, K.
Civillico, E. F.
Coburn, J.
Collinger, J.
Contreras-Vidal, J. L.
Denison, T.
Donoghue, J.
French, J.
Getzoff, N.
Hochberg, L. R.
Hoffmann, M.
Judy, J.
Kleitman, N.
Knaack, G.
Krauthamer, V.
Ludwig, K.
Moynahan, M.
Pancrazio, J. J.
Peckham, P. H.
Pena, C.
Pinto, V.
Ryan, T.
Saha, D.
Scharen, H.
Shermer, S.
Skodacek, K.
Takmakov, P.
Tyler, D.
Vasudevan, S.
Wachrathit, K.
Weber, D.
Welle, C. G.
Ye, M.
TI Brain-computer interface devices for patients with paralysis and
amputation: a meeting report
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
DE brain-computer interface; neuroprosthetic; regulation; translation;
medical device
ID PRIORITIES
AB Objective. The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) believes it is important to help stakeholders (e.g., manufacturers, health-care professionals, patients, patient advocates, academia, and other government agencies) navigate the regulatory landscape for medical devices. For innovative devices involving brain-computer interfaces, this is particularly important. Approach. Towards this goal, on 21 November, 2014, CDRH held an open public workshop on its White Oak, MD campus with the aim of fostering an open discussion on the scientific and clinical considerations associated with the development of brain-computer interface (BCI) devices, defined for the purposes of this workshop as neuroprostheses that interface with the central or peripheral nervous system to restore lost motor or sensory capabilities. Main results. This paper summarizes the presentations and discussions from that workshop. Significance. CDRH plans to use this information to develop regulatory considerations that will promote innovation while maintaining appropriate patient protections. FDA plans to build on advances in regulatory science and input provided in this workshop to develop guidance that provides recommendations for premarket submissions for BCI devices. These proceedings will be a resource for the BCI community during the development of medical devices for consumers.
C1 [Bowsher, K.; Getzoff, N.; Hoffmann, M.; Pena, C.; Pinto, V.; Saha, D.; Scharen, H.; Shermer, S.; Skodacek, K.; Wachrathit, K.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA.
[Civillico, E. F.; Coburn, J.; Knaack, G.; Krauthamer, V.; Takmakov, P.; Vasudevan, S.; Welle, C. G.; Ye, M.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA.
[Collinger, J.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
[Contreras-Vidal, J. L.] Univ Houston, Elect & Comp Engn, Houston, TX USA.
[Denison, T.] Medtronic Inc, Minneapolis, MN USA.
[Donoghue, J.; Hochberg, L. R.] Brown Univ, Brown Inst Brain Sci, Sch Engn, Providence, RI 02912 USA.
[French, J.] Neurotech Network, Tampa, FL 33623 USA.
[Hochberg, L. R.] Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Dept Vet Affairs Med Ctr, Providence, RI USA.
[Hochberg, L. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Judy, J.] Univ Florida, Coll Engn, Nanosci Inst Med & Engn Technol, Gainesville, FL 32611 USA.
[Kleitman, N.] Craig H Neilsen Fdn, Encino, CA USA.
[Ludwig, K.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Ludwig, K.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA.
[Moynahan, M.] Case Western Reserve Univ, Inst Funct Restorat, Cleveland, OH 44106 USA.
[Pancrazio, J. J.] Univ Texas Dallas, Bioengn, Dallas, TX 75230 USA.
[Peckham, P. H.; Tyler, D.] Case Western Reserve Univ, Sch Engn, Cleveland, OH 44106 USA.
[Ryan, T.] Adv Arm Dynam, Redono Beach, CA 90277 USA.
[Weber, D.] Def Adv Res Projects Agcy, Biol Technol Off, Arlington, VA USA.
RP Bowsher, K (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA.
RI Tyler, Dustin/C-7995-2015;
OI Tyler, Dustin/0000-0002-2298-8510; Welle, Cristin/0000-0001-8735-0983;
Pancrazio, Joseph/0000-0001-8276-3690; Takmakov,
Pavel/0000-0001-6591-0257
NR 21
TC 3
Z9 3
U1 4
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
EI 1741-2552
J9 J NEURAL ENG
JI J. Neural Eng.
PD APR
PY 2016
VL 13
IS 2
AR 023001
DI 10.1088/1741-2560/13/2/023001
PG 13
WC Engineering, Biomedical; Neurosciences
SC Engineering; Neurosciences & Neurology
GA DL5NM
UT WOS:000375683800004
PM 26924826
ER
PT J
AU Harris, LN
Ismaila, N
McShane, LM
Hayes, DF
AF Harris, Lyndsay N.
Ismaila, Nofisat
McShane, Lisa M.
Hayes, Daniel F.
TI Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for
Women With Early-Stage Invasive Breast Cancer: American Society of
Clinical Oncology Clinical Practice Guideline Summary
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
C1 Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Harris, Lyndsay N.] Amer Soc Clin Oncol, 2318 Mill Rd,Ste 800, Alexandria, VA 22314 USA.
NCI, Bethesda, MD 20892 USA.
Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Harris, LN (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Ste 800, Alexandria, VA 22314 USA.
NR 2
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD APR
PY 2016
VL 12
IS 4
BP 384
EP +
DI 10.1200/JOP.2016.010868
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DJ6LW
UT WOS:000374325700026
PM 26957642
ER
PT J
AU Roth, ME
O'Mara, AM
Seibel, NL
Dickens, DS
Langevin, AM
Pollock, BH
Freyer, DR
AF Roth, Michael E.
O'Mara, Ann M.
Seibel, Nita L.
Dickens, David S.
Langevin, Anne-Marie
Pollock, Brad H.
Freyer, David R.
TI Low Enrollment of Adolescents and Young Adults Onto Cancer Trials:
Insights From the Community Clinical Oncology Program
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID OLDER ADOLESCENTS; PARTICIPATION; INSTITUTE; CARE; CHALLENGES;
DIAGNOSIS; SURVIVAL
AB Purpose
Stagnant outcomes for adolescents and young adults (AYAs; 15 to 39 years old) with cancer are partly attributed to poor enrollment onto clinical trials. The National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP) was developed to improve clinical trial participation in the community setting, where AYAs are most often treated. Further, many CCOP sites had pediatric and medical oncologists with collaborative potential for AYA recruitment and care. For these reasons, we hypothesized that CCOP sites enrolled proportionately more AYAs than non-CCOP sites onto Children's Oncology Group (COG) trials.
Methods
For the 10-year period 2004 through 2013, the NCI Division of Cancer Prevention database was queried to evaluate enrollments into relevant COG studies. The proportional enrollment of AYAs at CCOP and non-CCOP sites was compared and the change in AYA enrollment patterns assessed. All sites were COG member institutions.
Results
Although CCOP sites enrolled a higher proportion of patients in cancer control studies than non-CCOP sites (3.5% v 1.8%; P < .001), they enrolled a lower proportion of AYAs (24.1% v 28.2%, respectively; P < .001). Proportional AYA enrollment at CCOP sites decreased during the intervals 2004 through 2008 and 2009 through 2013 (26.7% v 21.7%; P < .001).
Conclusion
Despite oncology practice settings that might be expected to achieve otherwise, CCOP sites did not enroll a larger proportion of AYAs in clinical trials than traditional COG institutions. Our findings suggest that the CCOP (now the NCI Community Oncology Research Program) can be leveraged for developing targeted interventions for overcoming AYA enrollment barriers.
C1 Albert Einstein Coll Med, Bronx, NY 10467 USA.
NCI, Bethesda, MD 20892 USA.
Helen DeVos Childrens Hosp Spectrum Hlth, Grand Rapids, MI USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
Univ Calif Davis, Davis, CA 95616 USA.
Univ So Calif, Los Angeles, CA USA.
RP Freyer, DR (reprint author), Childrens Hosp Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 USA.
EM DFreyer@CHLA.usc.edu
OI Dickens, David/0000-0001-8821-6022
FU NCI NIH HHS [K12 CA-132783-04, K12 CA132783, U10 CA098543, U10-CA98543]
NR 35
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD APR
PY 2016
VL 12
IS 4
BP E388
EP E395
DI 10.1200/JOP.2015.009084
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DJ6LW
UT WOS:000374325700005
PM 27026648
ER
PT J
AU Neely, AL
Thumbigere-Math, V
Somerman, MJ
Foster, BL
AF Neely, Anthony L.
Thumbigere-Math, Vivek
Somerman, Martha J.
Foster, Brian L.
TI A Familial Pattern of Multiple Idiopathic Cervical Root Resorption With
a 30-Year Follow-Up
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE Dental cementum; root resorption; tooth; tooth loss; tooth; resorption;
x-ray microtomography
ID TEETH; CLASSIFICATION; MANAGEMENT; DIAGNOSIS; ETIOLOGY
AB Background: Multiple idiopathic cervical root resorption (MICRR) is a rare entity distinct from pathologic root resorption that occurs as a result of several local and systemic factors. Methods: This report describes a familial pattern of MICRR, including a recently identified case and a 30-year follow-up on previously described cases.
Results: The previously reported father (aged 95 years) and son (aged 64 years), and the recently affected daughter (aged 61 years) recounted non-contributory medical history. The resorptive lesions were asymptomatic, unassociated with any predisposing factors, and first identified during the fourth to sixth decades of life. All tooth types were affected, with posterior teeth being affected earlier and with greater frequency; however, distal root surfaces were never affected. The resorptive lesions were progressive in nature, with additional teeth becoming involved as the condition was followed over time. In many instances, surrounding alveolar bone extended into the existing resorptive defects, but without clinical evidence of ankylosis. Gingival tissues, periodontal probing, and tooth mobility were within normal limits. Microcomputed tomography of extracted teeth demonstrated that the lesions were more extensive than clinically evident and rarely invaded the pulp chamber. Histologically, many resorptive lesions were noted along the cementum surface, with evidence of isolated cemental repair. Management of MICRR focused on restoring damaged root surfaces and extracting teeth with extensive root resorption.
Conclusions: MICRR is a challenging entity with unknown etiology and a lack of well-established preventive and management strategies. The familial pattern noted in this report necessitates future studies to investigate the role of genetic components in MICRR development.
C1 [Neely, Anthony L.] Univ Detroit Mercy, Sch Dent, Dept Periodontol & Dent Hyg, Detroit, MI 48208 USA.
[Thumbigere-Math, Vivek; Somerman, Martha J.; Foster, Brian L.] NIAMSD, Lab Oral & Connect Tissue Biol, NIH, Bethesda, MD 20892 USA.
[Foster, Brian L.] Ohio State Univ, Coll Dent, Biosci Div, Columbus, OH 43210 USA.
RP Neely, AL (reprint author), Univ Detroit Mercy, Sch Dent, Periodontol & Dent Hyg, 2700 Martin Luther King Jr Blvd, Detroit, MI 48208 USA.
EM neelya@udmercy.edu
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases at the National Institutes of Health,
Bethesda, Maryland
FX This work was supported in part by the Intramural Research Program of
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases at the National Institutes of Health, Bethesda, Maryland (MJS).
The authors thank Dr. Robert Nyberg and Dr. Jeffery R. Thomas, New Bern,
North Carolina, for providing clinical photos and radiographs related to
case 3. ALN and VT-M contributed equally to this study. The authors
report no conflicts of interest related to this study.
NR 43
TC 0
Z9 0
U1 0
U2 0
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD APR
PY 2016
VL 87
IS 4
BP 426
EP 433
DI 10.1902/jop.2015.150536
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DL7TK
UT WOS:000375842800013
PM 26561999
ER
PT J
AU Richardson, A
Fischer, KE
Speakman, JR
de Cabo, R
Mitchell, SJ
Peterson, CA
Rabinovitch, P
Chiao, YA
Taffet, G
Miller, RA
Renteria, RC
Bower, J
Ingram, DK
Ladiges, WC
Ikeno, Y
Sierra, F
Austad, SN
AF Richardson, Arlan
Fischer, Kathleen E.
Speakman, John R.
de Cabo, Rafael
Mitchell, Sarah J.
Peterson, Charlotte A.
Rabinovitch, Peter
Chiao, Ying A.
Taffet, George
Miller, Richard A.
Renteria, Rene C.
Bower, James
Ingram, Donald K.
Ladiges, Warren C.
Ikeno, Yuji
Sierra, Felipe
Austad, Steven N.
TI Measures of Healthspan as Indices of Aging in Mice-A Recommendation
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Healthspan; Lifespan; Physiological function; Age
ID CALORIC RESTRICTION; FRAILTY INDEX; C57BL/6 MICE; LIFE-SPAN; RAPAMYCIN
AB Over the past decade, a large number of discoveries have shown that interventions (genetic, pharmacological, and nutritional) increase the lifespan of invertebrates and laboratory rodents. Therefore, the possibility of developing antiaging interventions for humans has gone from a dream to a reality. However, it has also become apparent that we need more information than just lifespan to evaluate the translational potential of any proposed antiaging intervention to humans. Information is needed on how an intervention alters the "healthspan" of an animal, that is, how the physiological functions that change with age are altered. In this report, we describe the utility and the limitations of assays in mice currently available for measuring a wide range of physiological functions that potentially impact quality of life. We encourage investigators and reviewers alike to expect at minimum an overall assessment of health in several domains across several ages before an intervention is labeled as "increasing healthspan." In addition, it is important that investigators indicate any tests in which the treated group did worse or did not differ statistically from controls because overall health is a complex phenotype, and no intervention discovered to date improves every aspect of health. Finally, we strongly recommend that functional measurements be performed in both males and females so that sex differences in the rate of functional decline in different domains are taken into consideration.
C1 [Richardson, Arlan] Univ Oklahoma, Dept Geriatr Med, Hlth Sci Ctr, Norman, OK 73019 USA.
[Richardson, Arlan] Univ Alabama Birmingham, Oklahoma City VA Med Ctr, Birmingham, AL 35487 USA.
[Fischer, Kathleen E.; Austad, Steven N.] Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35487 USA.
[Speakman, John R.] Univ Aberdeen, Aberdeen AB9 1FX, Scotland.
[Speakman, John R.] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing, Peoples R China.
[de Cabo, Rafael; Mitchell, Sarah J.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Peterson, Charlotte A.] Univ Kentucky, Coll Hlth Sci, Lexington, KY 40506 USA.
[Rabinovitch, Peter; Chiao, Ying A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Taffet, George] Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX 77030 USA.
[Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Renteria, Rene C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Renteria, Rene C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Hlth Restorat, San Antonio, TX 78229 USA.
[Renteria, Rene C.] Univ Texas Hlth Sci Ctr San Antonio, Care Syst Management, San Antonio, TX 78229 USA.
[Renteria, Rene C.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA.
[Bower, James] Univ Calif Santa Cruz, Dept Comp Sci, Santa Cruz, CA 95064 USA.
[Ingram, Donald K.] Louisiana State Univ, Nutr Neurosci & Aging Lab, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 USA.
[Ladiges, Warren C.] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
[Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Richardson, Arlan; Sierra, Felipe] NIA, Biol Aging Program, Bethesda, MD 20892 USA.
RP Richardson, A (reprint author), Univ Oklahoma, Dept Geriatr Med, 975 NE 10th Street SLY BRC 1303, Oklahoma City, OK 73104 USA.
EM arlan-richardson@ouhsc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU NIA NIH HHS [P30 AG013319, P30 AG024824, R01 AG019899, R24 AG047115, T32
AG000057, U01 AG022303, U01 AG022307]
NR 20
TC 11
Z9 11
U1 4
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2016
VL 71
IS 4
BP 427
EP 430
DI 10.1093/gerona/glv080
PG 4
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4ZA
UT WOS:000374215400002
PM 26297941
ER
PT J
AU Stenholm, S
Koster, A
Valkeinen, H
Patel, KV
Bandinelli, S
Guralnik, JM
Ferrucci, L
AF Stenholm, Sari
Koster, Annemarie
Valkeinen, Heli
Patel, Kushang V.
Bandinelli, Stefania
Guralnik, Jack M.
Ferrucci, Luigi
TI Association of Physical Activity History With Physical Function and
Mortality in Old Age
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Physical activity; Physical performance; Disability; Mortality
ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; PERFORMANCE BATTERY;
MOBILITY LIMITATION; HEALTH; ADULTS; ADIPOSITY; INCHIANTI; VALIDITY;
COHORT
AB We examined whether physical activity in early adulthood, late midlife, and old age as well as cumulative physical activity history are associated with changes in physical functioning and mortality in old age.
Data are from participants aged 65 years or older enrolled in the InCHIANTI study who were followed up from 1998-2000 to 2007-2008 (n = 1,149). At baseline, participants recalled their physical activity levels at ages 20-40, 40-60, and in the previous year, and they were categorized as physically inactive, moderately active, and physically active. Physical performance was assessed with the Short Physical Performance Battery and self-reported mobility disability was evaluated at the 3-, 6- and 9-year follow-up. Mortality follow-up was assessed until the end of 2010.
Physical inactivity at baseline was associated with greater decline in Short Physical Performance Battery score (mean 9-year change: -2.72, 95% CI: -3.08, -2.35 vs -0.98, 95% -1.57, -0.39) and greater rate of incident mobility disability (hazard ratio 4.66, 95% CI 1.14-19.07) and mortality (hazard ratio 2.18, 95% CI 1.01-4.70) compared to physically active participants at baseline. Being physically active throughout adulthood was associated with smaller decline in physical performance as well as with lower risk of incident mobility disability and premature death compared with those who had been less active during their adult life.
Higher cumulative physical activity over the life course was associated with less decline in physical performance and reduced rate of incident mobility disability and mortality in older ages.
C1 [Stenholm, Sari] Univ Turku, Dept Publ Hlth, Lemminkaisenkatu 1, FI-20014 Turun, Finland.
[Stenholm, Sari] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Stenholm, Sari; Valkeinen, Heli] Natl Inst Hlth & Welf THL, Ageing Disabil & Functioning Unit, Helsinki, Finland.
[Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, NL-6200 MD Maastricht, Netherlands.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Florence, Italy.
[Guralnik, Jack M.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Stenholm, S (reprint author), Univ Turku, Dept Publ Hlth, Lemminkaisenkatu 1, FI-20014 Turun, Finland.
EM sari.stenholm@utu.fi
RI Koster, Annemarie/E-7438-2010
FU Academy of Finland [264944, 286294]; Intramural research program of the
National Institute on Aging, National Institutes of Health, Baltimore,
Maryland; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National
Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1,
N.1-AG-1-2111, N01-AG-5-0002, 1 Z01 AG001050-01]
FX This work was supported by grant from the Academy of Finland (264944 and
286294) and in part by the Intramural research program of the National
Institute on Aging, National Institutes of Health, Baltimore, Maryland.
The InCHIANTI study baseline (1998-2000) was supported as a "targeted
project" by the Italian Ministry of Health (ICS110.1/RF97.71) and in
part by the U.S. National Institute on Aging (263 MD 9164, 263 MD
821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S.
National Institute on Aging (N.1-AG-1-1, N.1-AG-1-2111); the InCHIANTI
Follow-up 2 study (2004-2006) was financed by the U.S. National
Institute on Aging (N01-AG-5-0002) and the InCHIANTI Follow-up 3 study
(2007-2008) was financed by the U.S. National Institute on Aging (1 Z01
AG001050-01).
NR 31
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U1 3
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2016
VL 71
IS 4
BP 496
EP 501
DI 10.1093/gerona/glv111
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4ZA
UT WOS:000374215400011
PM 26290538
ER
PT J
AU Chang, M
Snaedal, J
Einarsson, B
Bjornsson, S
Saczynski, JS
Aspelund, T
Garcia, M
Gudnason, V
Harris, TB
Launer, LJ
Jonsson, PV
AF Chang, Milan
Snaedal, Jon
Einarsson, Bjorn
Bjornsson, Sigurbjorn
Saczynski, Jane S.
Aspelund, Thor
Garcia, Melissa
Gudnason, Vilmundur
Harris, Tamara B.
Launer, Lenore J.
Jonsson, Palmi V.
TI The Association Between Midlife Physical Activity and Depressive
Symptoms in Late Life: Age Gene/Environment Susceptibility-Reykjavik
Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Mid-life physical activity; Aging; Depressive symptomatology; Cognitive
function
ID OLDER-ADULTS; GERIATRIC DEPRESSION; ALZHEIMER-DISEASE; CONTROLLED-TRIAL;
ELDERLY-MEN; EXERCISE; RISK; VALIDATION; EFFICACY; PEOPLE
AB Background. There is little evidence on the long-term association between physical activity (PA) and depressive symptoms in old age. We examined the association of midlife PA and depressive symptoms in late life.
Methods. A large community-based population residing in Reykjavik, Iceland, participated in a longitudinal study with an average of 25 years of follow up. Midlife PA was categorized as active and inactive groups (n = 4,140, Active = 1,292, Inactive = 2,848, mean age 52 +/- 7 years). The main outcome had six or higher depressive symptoms assessed by the 15-item Geriatric Depression scale. Participants who had a history of depression (n = 226), and were diagnosed with dementia (n = 393), and had incomplete cognitive data (n = 595) and incomplete analytical data (n = 422) were excluded. Level of weekly PA was ascertained by a questionnaire at midlife. Depressive symptoms were assessed on average 25 (+/-4) years later.
Results. After controlling for demographic and health-related risk factors, those who were active at midlife were less likely to have high level of depressive symptomatology (6 or higher Geriatric Depression scale scores, odds ratio = 0.58, 95% confidence interval: 0.41-0.83, p <.005) compared with those who were inactive in midlife. After full adjustment of three domains of late-life cognitive function the results remained significant (odds ratio = 0.61, 95% confidence interval: 0.43-0.86, p =.005).
Conclusion. Our study shows that midlife PA is associated with lower depressive symptoms 25 years later. Participating in regular PA in midlife may improve mental health in late life.
C1 [Chang, Milan; Snaedal, Jon; Einarsson, Bjorn; Bjornsson, Sigurbjorn; Jonsson, Palmi V.] Natl Univ Hosp Iceland, Iceland Gerongol Res Ctr, IS-101 Reykjavik, Iceland.
[Chang, Milan] Reykjavik Univ, Sch Sci & Engn, Dept Sport Sci, Reykjavik, Iceland.
[Snaedal, Jon; Gudnason, Vilmundur; Jonsson, Palmi V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Saczynski, Jane S.] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA USA.
[Saczynski, Jane S.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA.
[Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor] Univ Iceland, Fac Sci, Reykjavik, Iceland.
[Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] Natl Inst Aging, Lab Epidemiol & Populat Sci, Bethesda, MD USA.
RP Chang, M (reprint author), Natl Univ Hosp Iceland, Iceland Gerongol Res Ctr Landakot, IS-101 Reykjavik, Iceland.
EM changmilan@gmail.com
FU National Institutes of Health [N01-AG-12100]; National Institute on
Aging Intramural Research Program; Icelandic Heart Association;
Landspitali University Hospital; Icelandic Parliament
FX This study was funded by the National Institutes of Health (contract
N01-AG-12100), the National Institute on Aging Intramural Research
Program, the Icelandic Heart Association, Landspitali University
Hospital, and the Icelandic Parliament.
NR 38
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U1 4
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2016
VL 71
IS 4
BP 502
EP 507
DI 10.1093/gerona/glv196
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4ZA
UT WOS:000374215400012
PM 26525090
ER
PT J
AU McMahon, FJ
AF McMahon, Francis J.
TI Genetic association studies in psychiatry: time for pay-off
SO LANCET PSYCHIATRY
LA English
DT Editorial Material
ID SCHIZOPHRENIA; MUTATIONS; PROJECT
C1 [McMahon, Francis J.] NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP McMahon, FJ (reprint author), NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mcmahonf@mail.nih.gov
OI McMahon, Francis/0000-0002-9469-305X
FU National Institute of Mental Health
FX I declare no competing interests. This work was supported by the
Intramural Research Program of the National Institute of Mental Health.
This work was written as part of my official duties as a Government
employee. The views expressed in this article do not necessarily
represent the views of the National Institute of Mental Health, National
Institutes of Health, US Department of Health and Human Services, or the
US Government.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD APR
PY 2016
VL 3
IS 4
BP 309
EP 310
DI 10.1016/S2215-0366(16)00016-X
PG 3
WC Psychiatry
SC Psychiatry
GA DJ5NE
UT WOS:000374254600004
PM 26915513
ER
PT J
AU Noyce, AJ
Nalls, MA
AF Noyce, Alastair J.
Nalls, Mike A.
TI Mendelian Randomization the Key to Understanding Aspects of Parkinson's
Disease Causation?
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; Mendelian randomization; observational study;
causation
ID GLUCOCEREBROSIDASE MUTATIONS; SEQUENCE VARIANTS; RISK-FACTORS;
METAANALYSIS; ASSOCIATION; INSTRUMENTS
AB Parkinson's disease has multiple determinants and is associated with a wide range of exposures that appear to modify risk in traditional observational studies, including numerous lifestyle and environmental factors. Across other fields of medicine, Mendelian randomization has emerged as a powerful method to examine whether associations between exposures and disease outcomes are causal. Here we discuss the concept of Mendelian randomization, its potential relevance to Parkinson's disease, and suggest avenues through which the method could be employed to further understanding of the causal basis of Parkinson's disease. (c) 2015 International Parkinson and Movement Disorder Society
C1 [Noyce, Alastair J.] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 1PJ, England.
[Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Noyce, AJ (reprint author), UCL Inst Neurol, Reta Lila Weston Inst, 1 Wakefield St, London WC1N 1PJ, England.
EM a.noyce@ucl.ac.uk
FU Parkinson's UK [F-1201]
NR 32
TC 2
Z9 2
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR
PY 2016
VL 31
IS 4
BP 478
EP 483
DI 10.1002/mds.26492
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA DJ9PV
UT WOS:000374546300005
PM 26695521
ER
PT J
AU Comella, CL
Perlmutter, JS
Jinnah, HA
Waliczek, TA
Rosen, AR
Galpern, WR
Adler, CA
Barbano, RL
Factor, SA
Goetz, CG
Jankovic, J
Reich, SG
Rodriguez, RL
Severt, WL
Zurowski, M
Fox, SH
Stebbins, GT
AF Comella, Cynthia L.
Perlmutter, Joel S.
Jinnah, Hyder A.
Waliczek, Tracy A.
Rosen, Ami R.
Galpern, Wendy R.
Adler, Charles A.
Barbano, Richard L.
Factor, Stewart A.
Goetz, Christopher G.
Jankovic, Joseph
Reich, Stephen G.
Rodriguez, Ramon L.
Severt, William L.
Zurowski, Mateusz
Fox, Susan H.
Stebbins, Glenn T.
TI Clinimetric testing of the comprehensive cervical dystonia rating scale
SO MOVEMENT DISORDERS
LA English
DT Article
DE cervical dystonia; focal dystonia; rating scale; Toronto Western
Spasmodic Torticollis Rating Scale; Cervical Dystonia Impact Profile-58
ID QUALITY-OF-LIFE; BECK DEPRESSION INVENTORY; BOTULINUM TOXIN TREATMENT;
IMPACT PROFILE CDIP-58; SPASMODIC TORTICOLLIS; OUTCOME ASSESSMENT;
HOSPITAL ANXIETY; HEALTH; DETERMINANTS; VALIDATION
AB IntroductionThe aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale-2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile-58 as a quality of life measure.
MethodsTen dystonia experts rated subjects with cervical dystonia using the comprehensive scale. Clinimetric techniques assessed each module of the scale for reliability, item correlation, and factor structure.
ResultsThere were 208 cervical dystonia patients (73% women; age, 5910 years; duration, 15 +/- 12 years). Internal consistency of the motor severity subscale was acceptable (Cronbach's alpha=0.57). Item to total correlations showed that elimination of items with low correlations (<0.20) increased alpha to 0.71. Internal consistency estimates for the subscales for disability and pain were 0.88 and 0.95, respectively. The psychiatric screening scale had a Cronbach's alpha of 0.84 and satisfactory item to total correlations. When the subscales of the Toronto Western Spasmodic Torticollis Scale-2 were combined with the psychiatric screening scale, Cronbach's alpha was 0.88, and construct validity assessment demonstrated four rational factors: motor; disability; pain; and psychiatric disorders. The Cervical Dystonia Impact Profile-58 had an alpha of 0.98 and its construction was validated through a confirmatory factor analysis.
ConclusionsThe modules of the Comprehensive Cervical Dystonia Rating Scale are internally consistent with a logical factor structure. (c) 2016 International Parkinson and Movement Disorder Society
C1 [Comella, Cynthia L.; Waliczek, Tracy A.; Goetz, Christopher G.; Stebbins, Glenn T.] Rush Univ, Med Ctr, 1725 West Harrison St,Suite 755, Chicago, IL 60612 USA.
[Perlmutter, Joel S.] Washington Univ, Sch Med, St Louis, MO USA.
[Jinnah, Hyder A.; Rosen, Ami R.; Factor, Stewart A.] Emory Univ, Atlanta, GA 30322 USA.
[Galpern, Wendy R.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Adler, Charles A.] Mayo Clin, Scottsdale, AZ USA.
[Barbano, Richard L.] Univ Rochester, Rochester, NY USA.
[Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA.
[Reich, Stephen G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Rodriguez, Ramon L.] Univ Florida, Movement Disorders Ctr, Gainesville, FL USA.
[Severt, William L.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Zurowski, Mateusz; Fox, Susan H.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.
RP Comella, CL (reprint author), Rush Univ, Med Ctr, 1725 West Harrison St,Suite 755, Chicago, IL 60612 USA.
EM ccomella@rush.edu
RI zurowski, mateusz/D-1536-2010
OI zurowski, mateusz/0000-0002-6407-4629
FU NCATS NIH HHS [U54 TR001456]; NINDS NIH HHS [NS 065701, U54 NS065701,
R01 NS074343]
NR 42
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Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR
PY 2016
VL 31
IS 4
BP 563
EP 569
DI 10.1002/mds.26534
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DJ9PV
UT WOS:000374546300021
PM 26971359
ER
PT J
AU Kleinstreuer, NC
Sullivan, K
Allen, D
Edwards, S
Mendrick, DL
Embry, M
Matheson, J
Rowlands, JC
Munn, S
Maull, E
Casey, W
AF Kleinstreuer, Nicole C.
Sullivan, Kristie
Allen, David
Edwards, Stephen
Mendrick, Donna L.
Embry, Michelle
Matheson, Joanna
Rowlands, J. Craig
Munn, Sharon
Maull, Elizabeth
Casey, Warren
TI Adverse outcome pathways: From research to regulation scientific
workshop report
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE AOP; Workshop; Toxicology; Pathway; Regulatory; Quantitative;
Application; Acceptance; Criteria; Computational
ID DILUTION MASS-SPECTROMETRY; EARLY FISH DEVELOPMENT; THYROPEROXIDASE
INHIBITION; CONCEPTUAL-FRAMEWORK; VASCULAR DEVELOPMENT; TESTING
STRATEGY; DECISION-MAKING; IPCS FRAMEWORK; MODE; CONFIDENCE
AB An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Kleinstreuer, Nicole C.; Maull, Elizabeth; Casey, Warren] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA.
[Sullivan, Kristie] Phys Comm Responsible Med, Washington, DC USA.
[Allen, David] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Edwards, Stephen] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Mendrick, Donna L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Embry, Michelle] ILSI Hlth & Environm Sci Inst, Washington, DC USA.
[Matheson, Joanna] US Consumer Prod Safety Commiss, Rockville, MD USA.
[Rowlands, J. Craig] Dow Chem Co USA, Midland, MI 48674 USA.
[Munn, Sharon] Commiss European Communities, Joint Res Ctr, I-21020 Ispra, Italy.
RP Kleinstreuer, NC (reprint author), POB 13501, Res Triangle Pk, NC 27709 USA.
EM Nicole.kleinstreuer@nih.gov
OI Kleinstreuer, Nicole/0000-0002-7914-3682
FU federal funds from the NIEHS, NIH [HHSN273201400003C,
HHSN273201500010C]; NICEATM
FX The authors would like to thank all of the workshop presenters and
breakout group moderators, Hristo Aladjov for assisting in creation of
Fig. 3, George Daston for his contributions to the workshop steering
committee discussions, Catherine Sprankle for editorial comments,
NICEATM staff Michael Paris, Steven Morefield, Neepa Choksi, and
Catherine Sprankle for assistance with organizing and running the
workshop, and PCRM staff Arya Birdie and Mallory Huff for their
assistance with organizing the workshop. Nicole Kleinstreuer and David
Allen were supported by federal funds from the NIEHS, NIH under Contract
Numbers HHSN273201400003C and HHSN273201500010C to Integrated Laboratory
Systems, Inc., in support of NICEATM. The views represented in this
paper are those of the authors solely, and do not represent the official
policy of the U.S. EPA, FDA, NIH, or any other federal government
organization.
NR 45
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U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD APR
PY 2016
VL 76
BP 39
EP 50
DI 10.1016/j.yrtph.2016.01.007
PG 12
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA DL3DK
UT WOS:000375514200005
PM 26774756
ER
PT J
AU Reider, EE
Sims, BE
AF Reider, Eve E.
Sims, Belinda E.
TI Family-Based Preventive Interventions: Can the Onset of Suicidal
Ideation and Behavior Be Prevented?
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
AB Suicide is the second leading cause of death for youth aged 10-24. Research informed prevention efforts have the opportunity to decrease risk for suicidal ideation and behavior before it is manifested. Indeed, there is a small body of research findings demonstrating both proximal and distal effects of preventive interventions delivered in childhood and adolescence on suicidal ideation and/or behavior. These efforts build off of other secondary analyses of prevention research that has demonstrated benefits for multiple types of youth outcomes. This supplement provides proof of concept that family-based preventive interventions aimed at reducing a number of risk factors for suicide (e.g., substance use, externalizing, and internalizing behavior) can prevent suicidal ideation and behaviors.
C1 [Reider, Eve E.] NCCIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
[Sims, Belinda E.] NIDA, Bethesda, MD USA.
RP Reider, EE (reprint author), NCCIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM ereider@mail.nih.gov
FU Intramural NIH HHS [Z99 AT999999]
NR 15
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0363-0234
EI 1943-278X
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD APR
PY 2016
VL 46
SU 1
BP S3
EP S7
DI 10.1111/sltb.12252
PG 5
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DK1UL
UT WOS:000374699900001
PM 27094108
ER
PT J
AU Szabo, ST
Harry, GJ
Hayden, KM
Szabo, DT
Birnbaum, L
AF Szabo, Steven T.
Harry, G. Jean
Hayden, Kathleen M.
Szabo, David T.
Birnbaum, Linda
TI Comparison of Metal Levels between Postmortem Brain and Ventricular
Fluid in Alzheimer's Disease and Nondemented Elderly Controls
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE heavy metals; brain; cerebral spinal fluid; amyloid beta;
neurodegenerative disease
ID CEREBROSPINAL-FLUID; AMYLOID-BETA; NEURODEGENERATIVE DISORDERS;
OXIDATIVE STRESS; IRON LEVELS; COPPER; ZINC; ALUMINUM; PLASMA;
HIPPOCAMPUS
AB An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer's disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance.
C1 [Szabo, Steven T.] Vet Adm Med Ctr, Mental Hlth Serv Line, Durham, NC 27705 USA.
[Szabo, Steven T.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA.
[Harry, G. Jean] NIEHS, Neurotoxicol Grp, Natl Toxicol Program Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Hayden, Kathleen M.] Duke Univ, Med Ctr, Joseph & Kathleen ADRC, Dept Psychiat & Behav Sci, Durham, NC 27705 USA.
[Szabo, David T.] RAI Serv Co, Winston Salem, NC 27102 USA.
[Birnbaum, Linda] NCI, NIH, Res Triangle Pk, NC 27709 USA.
[Hayden, Kathleen M.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA.
RP Szabo, ST (reprint author), Vet Adm Med Ctr, Mental Hlth Serv Line, Durham, NC 27705 USA.; Szabo, ST (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA.
EM steven.szabo@duke.edu
FU NTP [HHSN27320100003C]; Division of Intramural Research and Division
National Toxicology Program, National Institute of Environmental Health
Sciences [1Z01ES101623, ES021164]; National Cancer Institute [ZIA BC
011476]; Joseph and Kathleen Bryan Alzheimer's Disease Research Center
[NIA P30AG028377]
FX NTP contract HHSN27320100003C to Research Triangle Institute; the
Division of Intramural Research and Division National Toxicology
Program, National Institute of Environmental Health Sciences, no.
1Z01ES101623, ES021164; the National Cancer Institute no. ZIA BC 011476;
the Joseph and Kathleen Bryan Alzheimer's Disease Research Center grant
NIA P30AG028377.
NR 60
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U1 13
U2 20
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD APR
PY 2016
VL 150
IS 2
BP 292
EP 300
DI 10.1093/toxsci/kfv325
PG 9
WC Toxicology
SC Toxicology
GA DJ5ET
UT WOS:000374230300005
PM 26721301
ER
PT J
AU Su, TP
Su, TC
Nakamura, Y
Tsai, SY
AF Su, Tsung-Ping
Su, Tzu-Chieh
Nakamura, Yoki
Tsai, Shang-Yi
TI The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOPLASMIC-RETICULUM MEMBRANE;
GUINEA-PIG BRAIN; MOUSE MODEL; MECHANICAL ALLODYNIA; OPIOID ANALGESIA;
NEUROPATHIC PAIN; NMDA RECEPTOR; ALZHEIMERS-DISEASE; P38 MAPK
AB The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems.
C1 [Su, Tsung-Ping; Su, Tzu-Chieh; Nakamura, Yoki; Tsai, Shang-Yi] NIDA, Cellular Pathobiol Sect, Integrat Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS, Baltimore, MD 21224 USA.
RP Su, TP (reprint author), NIDA, Cellular Pathobiol Sect, Integrat Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS, Baltimore, MD 21224 USA.
EM TSU@intra.nida.nih.gov
RI Nakamura, Yoki/P-7785-2016
OI Nakamura, Yoki/0000-0001-9226-676X
FU National Institute on Drug Abuse; Dragon Gate Program of the Ministry of
Science and Technology of Taiwan (MOST) [105-2911-1-038 -503]; Japanese
Society for Promotion of Sciences
FX This work is supported by the Intramural Research Program of the
National Institute on Drug Abuse. T-C.S. is supported, in part, by the
Dragon Gate Program of the Ministry of Science and Technology of Taiwan
(MOST #105-2911-1-038 -503). Y. N. is supported in part by the Japanese
Society for Promotion of Sciences.
NR 140
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U2 13
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD APR
PY 2016
VL 37
IS 4
BP 262
EP 278
DI 10.1016/j.tips.2016.01.003
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK1XK
UT WOS:000374708300006
PM 26869505
ER
PT J
AU Bilgel, M
An, Y
Zhou, Y
Wong, DF
Prince, JL
Ferrucci, L
Resnick, SM
AF Bilgel, Murat
An, Yang
Zhou, Yun
Wong, Dean F.
Prince, Jerry L.
Ferrucci, Luigi
Resnick, Susan M.
TI Individual estimates of age at detectable amyloid onset for risk factor
assessment
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE APOE; Pittsburgh compound B; PET; Amyloid imaging; Age at onset
ID APOLIPOPROTEIN-E EPSILON-4; NORMAL OLDER-ADULTS; ALZHEIMER-DISEASE; APOE
GENOTYPE; A-BETA; LIFE-SPAN; BRAIN; DEPOSITION; ASSOCIATION; BIOMARKERS
AB Introduction: Individualized estimates of age at detectable amyloid-beta (A beta) accumulation, distinct from amyloid positivity, allow for analysis of onset age of A beta accumulation as an outcome measure to understand risk factors.
Methods: Using longitudinal Pittsburgh compound B (PiB) positron emission tomography data from Baltimore Longitudinal Study of Aging, we estimated the age at which each PiB+ individual began accumulating A beta. We used survival analysis methods to quantify risk of accumulating A beta and differences in onset age of A beta accumulation in relation to APOE epsilon 4 status and sex among 36 APOE epsilon 4 carriers and 83 noncarriers.
Results: Age at onset of A beta accumulation for the APOE epsilon 4- and epsilon 4+ groups was 73.1 and 60.7, respectively. APOE epsilon 4 positivity conferred a threefold risk of accumulating A beta after adjusting for sex and education.
Discussion: Estimation of onset age of amyloid accumulation may help gauge treatment efficacy in interventions to delay symptom onset in Alzheimer's disease. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
C1 [Bilgel, Murat; An, Yang; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Bilgel, Murat; Prince, Jerry L.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
[Zhou, Yun; Wong, Dean F.; Prince, Jerry L.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA.
[Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA.
[Ferrucci, Luigi] NIA, Translat Gerontol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Bilgel, M (reprint author), NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.; Bilgel, M (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
EM murat.bilgel@nih.gov
OI Bilgel, Murat/0000-0001-5042-7422
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health. The
authors are grateful to the BLSA participants and staff for their
dedication to these studies and the staff of the Johns Hopkins PET
facility for their assistance. The authors thank Brieana Viscomi and
Wendy Elkins for assistance with coordination and data collection for
the PET studies.
NR 43
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD APR
PY 2016
VL 12
IS 4
BP 373
EP 379
DI 10.1016/j.jalz.2015.08.166
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DK7YC
UT WOS:000375142000001
PM 26588863
ER
PT J
AU Mwachiro, MM
Burgert, SL
Lando, J
Chepkwony, R
Bett, C
Bosire, C
Abnet, CC
Githanga, J
Waweru, W
Giffen, CA
Murphy, G
White, RE
Topazian, MD
Dawsey, SM
AF Mwachiro, Michael M.
Burgert, Stephen L.
Lando, Justus
Chepkwony, Robert
Bett, Collins
Bosire, Claire
Abnet, Christian C.
Githanga, Jessie
Waweru, Wairimu
Giffen, Carol A.
Murphy, Gwen
White, Russell E.
Topazian, Mark D.
Dawsey, Sanford M.
TI Esophageal Squamous Dysplasia is Common in Asymptomatic Kenyans: A
Prospective, Community-Based, Cross-Sectional Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID HIGH-RISK AREA; CELL CARCINOMA; FOLLOW-UP; PRECANCEROUS LESIONS;
CYTOLOGIC DETECTION; CANCER STATISTICS; CHINA; LINXIAN; POPULATION; IRAN
AB OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is endemic in east Africa and is a leading cause of cancer death among Kenyans. The asymptomatic precursor lesion of ESCC is esophageal squamous dysplasia (ESD). We aimed to determine the prevalence of ESD in asymptomatic adult residents of southwestern Kenya.
METHODS: In this prospective, community-based, cross-sectional study, 305 asymptomatic adult residents completed questionnaires and underwent video endoscopy with Lugol's iodine chromoendoscopy and mucosal biopsy for detection of ESD.
RESULTS: Study procedures were well tolerated, and there were no adverse events. The overall prevalence of ESD was 14.4% (95% confidence interval (CI): 10-19%), including 11.5% with low-grade dysplasia and 2.9% with high-grade dysplasia. The prevalence of ESD was >20% among men aged >50 years and women aged >60 years. Residence location was significantly associated with ESD (Zone A adjusted odds ratio (OR) 2.37, 95% CI: 1.06-5.30 and Zone B adjusted OR 2.72, 95% CI: 1.12-6.57, compared with Zone C). Iodine chromoendoscopy with biopsy of unstained lesions was more sensitive than white-light endoscopy or random mucosal biopsy for detection of ESD and had 67% sensitivity and 70% specificity.
CONCLUSIONS: ESD is common among asymptomatic residents of southwestern Kenya and is especially prevalent in persons aged >50 years and those living in particular local regions. Lugol's iodine chromoendoscopy is necessary for detection of most ESD but has only moderate sensitivity and specificity in this setting. Screening for ESD is warranted in this high-risk population, and endoscopic screening of Kenyans is feasible, safe, and acceptable, but more accurate and less invasive screening tests are needed.
C1 [Mwachiro, Michael M.; Burgert, Stephen L.; Lando, Justus; Chepkwony, Robert; Bett, Collins; White, Russell E.] Tenwek Hosp, POB 39, Bomet 20400, Kenya.
[Bosire, Claire; Abnet, Christian C.; Murphy, Gwen; Dawsey, Sanford M.] NCI, Bethesda, MD 20892 USA.
[Githanga, Jessie; Waweru, Wairimu] Univ Nairobi, Dept Pathol, Nairobi, Kenya.
[Giffen, Carol A.] Informat Management Serv Inc, Calverton, MD USA.
[Topazian, Mark D.] Mayo Clin, Rochester, MN USA.
RP Mwachiro, MM (reprint author), Tenwek Hosp, POB 39, Bomet 20400, Kenya.
EM deche2002@yahoo.com
RI Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; Mwachiro,
Michael/0000-0002-3779-5324
FU BIG CAT (Beginning Investigator Grant for Catalytic Research) grant from
the African Organization for Research and Training in Cancer (AORTIC);
US National Cancer Institute (NCI)
FX This work was supported by BIG CAT (Beginning Investigator Grant for
Catalytic Research) grant from the African Organization for Research and
Training in Cancer (AORTIC) and the US National Cancer Institute (NCI).
NR 24
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U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD APR
PY 2016
VL 111
IS 4
BP 500
EP 507
DI 10.1038/ajg.2016.26
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DL2DE
UT WOS:000375442300016
PM 26902228
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI RAISE-ing Our Expectations for First-Episode Psychosis
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID TRIAL
C1 [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA.
EM insel@mail.nih.gov
NR 4
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U1 3
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD APR
PY 2016
VL 173
IS 4
BP 311
EP 312
DI 10.1176/appi.ajp.2015.15091204
PG 2
WC Psychiatry
SC Psychiatry
GA DK9ZH
UT WOS:000375290400001
PM 26481175
ER
PT J
AU Kane, JM
Robinson, DG
Schooler, NR
Mueser, KT
Penn, DL
Rosenheck, RA
Addington, J
Brunette, MF
Correll, CU
Estroff, SE
Marcy, P
Robinson, J
Meyer-Kalos, PS
Gottlieb, JD
Glynn, SM
Lynde, DW
Pipes, R
Kurian, BT
Miller, AL
Azrin, ST
Goldstein, AB
Severe, JB
Lin, HQ
Sint, KJ
John, M
Heinssen, RK
AF Kane, John M.
Robinson, Delbert G.
Schooler, Nina R.
Mueser, Kim T.
Penn, David L.
Rosenheck, Robert A.
Addington, Jean
Brunette, Mary F.
Correll, Christoph U.
Estroff, Sue E.
Marcy, Patricia
Robinson, James
Meyer-Kalos, Piper S.
Gottlieb, Jennifer D.
Glynn, Shirley M.
Lynde, David W.
Pipes, Ronny
Kurian, Benji T.
Miller, Alexander L.
Azrin, Susan T.
Goldstein, Amy B.
Severe, Joanne B.
Lin, Haiqun
Sint, Kyaw J.
John, Majnu
Heinssen, Robert K.
TI Comprehensive Versus Usual Community Care for First-Episode Psychosis:
2-Year Outcomes From the NIMH RAISE Early Treatment Program
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; NEGATIVE SYNDROME SCALE; 5-YEAR FOLLOW-UP;
EARLY INTERVENTION; UNITED-STATES; UNTREATED PSYCHOSIS; STANDARD
TREATMENT; COST-EFFECTIVENESS; MULTICENTER TRIAL; SPECIALIZED CARE
AB Objective: The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life.
Method: Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and <= 6 months of antipsychotic treatment (N=404) were enrolled and followed for >= 2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.
Results: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of,74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups.
Conclusions: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.
C1 [Kane, John M.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA.
Hofstra North Shore Long Isl Jewish Sch Med, Dept Psychiat, Hempstead, NY USA.
Hofstra North Shore Long Isl Jewish Sch Med, Dept Mol Med, Hempstead, NY USA.
Hofstra Univ, Dept Math, Hempstead, NY 11550 USA.
Feinstein Inst Med Res, Manhasset, NY USA.
Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA.
Boston Univ, Ctr Psychiat Rehabil, Dept Occupat Therapy, Boston, MA 02215 USA.
Boston Univ, Ctr Psychiat Rehabil, Dept Psychiat, Boston, MA 02215 USA.
Boston Univ, Ctr Psychiat Rehabil, Dept Psychol, Boston, MA 02215 USA.
Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
Univ N Carolina, Dept Social Med, Chapel Hill, NC USA.
Australian Catholic Univ, Sch Psychol, Melbourne, Vic, Australia.
Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
Yale Univ, Sch Publ Hlth, New Haven, CT USA.
Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB, Canada.
Dartmouth Coll, Geisel Sch Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
Bur Behav Hlth, New Hampshire Dept Hlth & Human Serv, Concord, NH USA.
Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
Univ Minnesota, Sch Social Work, Minnesota Ctr Chem & Mental Hlth, St Paul, MN 55108 USA.
Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
NIMH, Div Serv & Intervent Res, Rockville, MD 20857 USA.
RP Kane, JM (reprint author), North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA.
EM psychiatry@nshs.edu
FU American Recovery and Reinvestment Act and from NIMH
[HHSN271200900019C]; NIMH Advanced Centers for Intervention and/or
Services Research award [P30MH090590]; Bristol-Myers Squibb; Janssen;
Otsuka; Genentech; Neurocrine; Alkermes; Johnson and Johnson; Novo
Nordisk; Takeda; Evotec; Forest; Naurex; Pfizer; Rexahn; Targacept
FX This work has been funded in whole or in part with funds from the
American Recovery and Reinvestment Act and from NIMH under contract
HHSN271200900019C. Additional support for these analyses was provided by
an NIMH Advanced Centers for Intervention and/or Services Research award
(P30MH090590) to Dr. Kane.; Dr. Kane has been a consultant for Alkermes,
Amgen, Bristol-Myers Squibb, Eli Lilly, EnVivo Pharmaceuticals (Forum),
Forest, Genentech, H. Lundbeck, Intra-Cellular Therapies, Janssen
Pharmaceutica, Johnson and Johnson, Merck, Novartis, Otsuka, Pierre
Fabre, Reviva, Roche, Sunovion, and Teva; he has received honoraria for
lectures from Bristol-Myers Squibb, Genentech, Janssen, Lundbeck, and
Otsuka; and he is a shareholder in MedAvante and in Vanguard Research
Group. Dr. Robinson has been a consultant to Asubio, Otsuka, and Shire;
and he has received grants from Bristol-Myers Squibb, Janssen, and
Otsuka. Dr. Schooler has served on advisory boards or as a consultant
for Abbott, Alkermes, Amgen, Eli Lilly, Forum(formerly EnVivo), Janssen
Psychiatry, Roche, and Sunovion; she has received grant or research
support from Genentech, Neurocrine, and Otsuka; and she has served on a
data monitoring board for Shire and on the faculty of the Lundbeck
International Neuroscience Foundation. Dr. Brunette has received grant
support from Alkermes. Dr. Correll has been a consultant or adviser to
or has received honoraria from AbbVie, Actavis, Actelion, Alexza,
Alkermes, Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, Gerson
Lehrman Group, Intra-Cellular Therapies, Janssen, Johnson and Johnson,
Lundbeck, MedAvante, Medscape, Merck, Otsuka, Pfizer, ProPhase, Reviva,
Roche, Sunovion, Supernus, Takeda, Teva, and Vanda; and he has received
grant support from Bristol-Myers Squibb, Janssen, Johnson and Johnson,
Novo Nordisk, Otsuka, and Takeda. Ms. Marcy is a shareholder in Pfizer.
Mr. Robinson has received grant support from Otsuka and is a shareholder
in Pfizer. Dr. Kurian has received grant support from Evotec, Forest,
Johnson and Johnson, Naurex, Pfizer, Rexahn, and Targacept. Dr. Miller
has received payments for serving on a data monitoring committee for a
study sponsored by Otsuka. The authors and their associates provide
training and consultation about implementing NAVIGATE treatment that can
include compensation. These activities started only after data
collection for the article was completed. At the time of publication,
Dr. Meyer-Kalos, Dr. Glynn, and Dr. Robinson had received compensation
for these activities. The other authors report no financial
relationships with commercial interests.
NR 38
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U2 15
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD APR
PY 2016
VL 173
IS 4
BP 362
EP 372
DI 10.1176/appi.ajp.2015.15050632
PG 11
WC Psychiatry
SC Psychiatry
GA DK9ZH
UT WOS:000375290400011
PM 26481174
ER
PT J
AU Sheng, Y
Filichia, E
Shick, E
Preston, KL
Phillips, KA
Cooperman, L
Lin, ZC
Tesar, P
Hoffer, BJ
Luo, Y
AF Sheng, Yang
Filichia, Emily
Shick, Elizabeth
Preston, Kenzie L.
Phillips, Karran A.
Cooperman, Leslie
Lin, Zhicheng
Tesar, Paul
Hoffer, Barry J.
Luo, Yu
TI Lower Dopamine D-2 Receptor Expression Levels in Human Dopaminergic
Neurons Derived From Opioid-Dependent iPSCs
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Letter
C1 [Sheng, Yang] Case Western Reserve Univ, Sch Med, Dept Neurol Surg, Cleveland, OH 44106 USA.
Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA.
Case Western Reserve Univ, Sch Med, Dept Genome Sci, Cleveland, OH 44106 USA.
NIDA, Intramural Res Program, Clin Trials Treatment Branch, Baltimore, MD USA.
NIDA, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD USA.
NIDA, Cellular Neurobiol Branch, Baltimore, MD USA.
Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA.
RP Sheng, Y (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurol Surg, Cleveland, OH 44106 USA.
FU Intramural NIH HHS; NIDA NIH HHS [R21DA032962, R21 DA032962, R01
DA021409, DA021409]
NR 6
TC 1
Z9 1
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD APR
PY 2016
VL 173
IS 4
BP 429
EP 431
DI 10.1176/appi.ajp.2015.15121545
PG 3
WC Psychiatry
SC Psychiatry
GA DK9ZH
UT WOS:000375290400018
PM 27035534
ER
PT J
AU Ziegler, TR
May, AK
Hebbar, G
Easley, KA
Griffith, DP
Dave, N
Collier, BR
Cotsonis, GA
Hao, L
Leong, T
Manatunga, AK
Rosenberg, ES
Jones, DP
Martin, GS
Jensen, GL
Sax, HC
Kudsk, KA
Galloway, JR
Blumberg, HM
Evans, ME
Wischmeyer, PE
AF Ziegler, Thomas R.
May, Addison K.
Hebbar, Gautam
Easley, Kirk A.
Griffith, Daniel P.
Dave, Nisha
Collier, Bryan R.
Cotsonis, George A.
Hao, Li
Leong, Traci
Manatunga, Amita K.
Rosenberg, Eli S.
Jones, Dean P.
Martin, Gregory S.
Jensen, Gordon L.
Sax, Harry C.
Kudsk, Kenneth A.
Galloway, John R.
Blumberg, Henry M.
Evans, Mary E.
Wischmeyer, Paul E.
TI Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in
Surgical ICU Patients: An American Multicenter Randomized Controlled
Trial
SO ANNALS OF SURGERY
LA English
DT Article
DE critical care; critical illness; glutamine; hospital-acquired infection;
nutrition support; parenteral nutrition
ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; MAJOR ABDOMINAL-SURGERY;
ACUTE LUNG INJURY; DOUBLE-BLIND; CRITICAL ILLNESS; MECHANICAL
VENTILATION; NITROGEN-BALANCE; CLINICAL-TRIAL; ORGAN FAILURE
AB Objective:To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients.Summary Background Data:GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients.Methods:A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5g/kg/d amino acids (AAs) and energy at 1.3x estimated basal energy expenditure]. Controls (n=75) received standard GLN-free PN (STD-PN); the GLN group (n=75) received PN containing alanyl-GLN dipeptide (0.5g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints.Results:Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P=0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P=0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P=0.73). Other clinical outcomes and adverse events were similar.Conclusions:PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.
C1 [Ziegler, Thomas R.; Hebbar, Gautam; Hao, Li] Emory Univ, Sch Med, Dept Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA.
[Ziegler, Thomas R.; Jones, Dean P.; Galloway, John R.] Emory Univ, Sch Med, Ctr Clin & Mol Nutr, Atlanta, GA USA.
[Ziegler, Thomas R.; Hebbar, Gautam; Griffith, Daniel P.; Dave, Nisha; Galloway, John R.] Emory Univ Hosp, Nutr & Metab Support Serv, Suite GG-23,1364 Clifton Rd, Atlanta, GA 30322 USA.
[May, Addison K.; Collier, Bryan R.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA.
[Easley, Kirk A.; Cotsonis, George A.; Leong, Traci; Manatunga, Amita K.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Collier, Bryan R.] Virginia Tech, Inst Caril Sch Med, Dept Surg, Roanoke, VA USA.
[Rosenberg, Eli S.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Martin, Gregory S.] Emory Univ, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA.
[Jensen, Gordon L.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Sax, Harry C.] Miriam Hosp, Dept Surg, Providence, RI 02906 USA.
[Sax, Harry C.] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA.
[Kudsk, Kenneth A.] Univ Wisconsin, Sch Med, Dept Surg, Madison, WI USA.
[Kudsk, Kenneth A.] Univ Wisconsin, Sch Publ Hlth, Madison, WI USA.
[Galloway, John R.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA.
[Blumberg, Henry M.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA.
[Blumberg, Henry M.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
[Evans, Mary E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Wischmeyer, Paul E.] Univ Colorado, Sch Med, Dept Anesthesiol, Aurora, CO USA.
RP Ziegler, TR (reprint author), Emory Univ Hosp, Atlanta Clin & Translat Sci Inst, Suite GG-23,1364 Clifton Rd, Atlanta, GA 30322 USA.
EM tzieg01@emory.edu
RI Easley, Kirk/K-6910-2015
OI Easley, Kirk/0000-0003-4419-2617
FU National Institutes of Health [U01 DK069322, K24 DK096574, UL1 TR000454,
K23 RR018379, R01 GM078312]; Fresenius Kabi
FX This work was supported, in part, by National Institutes of Health
grants U01 DK069322 and K24 DK096574 (T.R.Z.), UL1 TR000454 (Atlanta
Clinical and Translational Science Institute), K23 RR018379 and R01
GM078312 (P.E.W.) and an investigator-initiated grant from Fresenius
Kabi (T.R.Z.). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 56
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Z9 8
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD APR
PY 2016
VL 263
IS 4
BP 646
EP 655
DI 10.1097/SLA.0000000000001487
PG 10
WC Surgery
SC Surgery
GA DK2YZ
UT WOS:000374782700014
PM 26501700
ER
PT J
AU Illei, PB
Alewine, C
Zahurak, M
Cowan, ML
Montgomery, E
Hassan, R
Xiang, LM
Pastan, I
Kelly, RJ
AF Illei, Peter B.
Alewine, Christine
Zahurak, Marianna
Cowan, Morgan L.
Montgomery, Elizabeth
Hassan, Raffit
Xiang, Laiman
Pastan, Ira
Kelly, Ronan J.
TI Mesothelin Expression in Advanced Gastroesophageal Cancer Represents a
Novel Target for Immunotherapy
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE carcinoma; expression; gastric; gastroesophageal; immunotherapy
mesothelin; target
ID GASTRIC-CANCER; JUNCTION ADENOCARCINOMA; ANTITUMOR-ACTIVITY; SERUM
MESOTHELIN; IMMUNOTOXIN SS1P; OVARIAN CANCERS; BREAST-CANCER;
COMBINATION; VALIDATION; CISPLATIN
AB The identification of new therapeutic targets is of profound importance if we are to improve outcomes in gastroesophageal cancer. This study assessed the rate of mesothelin expression in tumors of western patients with upper gastrointestinal tract carcinomas. In addition, the AGS gastric cancer cell line was tested for sensitivity to SS1(dsFv)PE38, a mesothelin-targeting immunotoxin. Previously constructed tissue microarrays containing samples from 127 patients with gastroesophageal adenocarcinomas were examined by immunohistochemistry (IHC) for mesothelin expression. Labeling for HER2-neu, E-cadherin, and c-met were also assessed. Tumors were considered positive for mesothelin if at least moderate cytoplasmic/membranous or luminal staining was present in minimum 10% of the neoplastic cells. The AGS gastric cancer cell line was assessed for surface mesothelin expression by flow cytometry and the viability of cells treated with SS1P was measured. Gastroesophageal cancers were mesothelin positive in 64 of 127 tumors [50.4%; 95% confidence interval (CI), 41.4%-59.4%], whereas only 9 carcinomas (7.1%; 95% CI, 3.3%-13.0%) were HER2-neu IHC 3+ positive and 8 (6.6%; 95% CI, 2.9%-12.5%) were c-met positive. Mesothelin expression increased from stage I to stage IV tumors (37.5% to 56.3%, respectively, P=0.10). The AGS gastric cancer cell line was sensitive to the immunotoxin with an EC50 value in the low picomolar range (0.4 ng/mL). A gastric cancer cell line derived from a western patient was exquisitely sensitive to the mesothelin-targeted immunotoxin SS1P. Clinical trials involving novel mesothelin targeted immunotherapeutics in gastroesophageal cancer are currently in development.
C1 [Illei, Peter B.; Cowan, Morgan L.; Montgomery, Elizabeth] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Kelly, Ronan J.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 406 N Broadway, Baltimore, MD 21287 USA.
[Alewine, Christine; Zahurak, Marianna; Hassan, Raffit; Xiang, Laiman; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kelly, RJ (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 406 N Broadway, Baltimore, MD 21287 USA.
EM rkelly25@jhmi.edu
FU Sidney Kimmel Comprehensive Cancer Center Core Grant [P30 CA006973];
Intramural Research Program of the NIH; National Cancer Institute,
Center for Cancer Research
FX Supported in part by the Sidney Kimmel Comprehensive Cancer Center Core
Grant P30 CA006973 and by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 30
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Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1541-2016
EI 1533-4058
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD APR
PY 2016
VL 24
IS 4
BP 246
EP 252
DI 10.1097/PAI.0000000000000292
PG 7
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA DK6MH
UT WOS:000375037700005
PM 26894650
ER
PT J
AU Katz, JL
Hong, WC
Hiranita, T
Su, TP
AF Katz, Jonathan L.
Hong, Weimin C.
Hiranita, Takato
Su, Tsung-Ping
TI A role for sigma receptors in stimulant self-administration and
addiction
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Review
DE chaperone protein; cocaine; drug abuse; methamphetamine; reinforcing
effects; self-administration; sigma receptors
ID CONDITIONED PLACE PREFERENCE; LIPID RAFT RECONSTITUTION; UNFOLDED
PROTEIN RESPONSE; DOPAMINE TRANSPORTER; ENDOPLASMIC-RETICULUM; PC12
CELLS; UPTAKE INHIBITORS; COCAINE BINDING; LIGAND; BRAIN
AB Sigma-1 receptors (sigma 1Rs) are structurally unique intracellular proteins that function as chaperones. sigma 1Rs translocate from the mitochondria-associated membrane to other subcellular compartments, and can influence a host of targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Drugs binding to sigma Rs can induce or block the actions of sigma Rs. Studies indicate that stimulant self-administration induces the reinforcing effects of sigma R agonists, because of dopamine transporter actions. Once established, the reinforcing effects of sigma R agonists are independent of dopaminergic mechanisms traditionally thought to be critical to the reinforcing effects of stimulants. Self-administered doses of sigma R agonists do not increase dopamine concentrations in the nucleus accumbens shell, a transmitter and brain region considered important for the reinforcing effects of abused drugs. However, self-administration of sigma R agonists is blocked by sigma R antagonists. Several effects of stimulants have been blocked by sigma R antagonists, including the reinforcing effects, assessed by a place-conditioning procedure. However, the self-administration of stimulants is largely unaffected by sigma R antagonists, indicating fundamental differences in the mechanisms underlying these two procedures used to assess the reinforcing effects. When sigma R antagonists are administered in combination with dopamine uptake inhibitors, an effective and specific blockade of stimulant self-administration is obtained. Actions of stimulant drugs related to their abuse induce unique changes in sigma R activity and the changes induced potentially create redundant and, once established, independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and sigma R proteins produces a selective antagonism of stimulant self-administration, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Katz, Jonathan L.; Hong, Weimin C.; Hiranita, Takato] NIDA, Psychobiol, Dept Hlth & Human Serv, Baltimore, MD USA.
[Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
OI Katz, Jonathan/0000-0002-1068-1159
FU National Institute on Drug Abuse Intramural Research Program; NIDA IRP;
Japan Society for the Promotion of Science
FX The authors thank Gianluigi Tanda, Paul L. Soto, Christopher R. McCurdy,
and Theresa Kopajtic for their many contributions to the experiments,
conceptual approaches, and all-around collegiality. The staff of the
Medicinal Chemistry Section of the NIDA Intramural Research Program
kindly synthesized some of the compounds used in the studies described.
Funding for the experiments originating in our laboratories was provided
by the National Institute on Drug Abuse Intramural Research Program.
Takato Hiranita was supported in part by the NIDA IRP and by a
fellowship from the Japan Society for the Promotion of Science. Subjects
used in the studies published from the NIDA Intramural Research Program
were maintained in facilities fully accredited by the American
Association for the Accreditation of Laboratory Animal Care, and those
experiments were conducted in accordance with the guidelines of the
institute's Animal Care and Use Committee.
NR 98
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U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD APR
PY 2016
VL 27
IS 2-3
SI SI
BP 100
EP 115
DI 10.1097/FBP.0000000000000209
PG 16
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA DK4MQ
UT WOS:000374892900003
PM 26650253
ER
PT J
AU Radke, AK
Zlebnik, NE
Holtz, NA
Carroll, ME
AF Radke, Anna K.
Zlebnik, Natalie E.
Holtz, Nathan A.
Carroll, Marilyn E.
TI Cocaine-induced reward enhancement measured with intracranial
self-stimulation in rats bred for low versus high saccharin intake
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE cocaine; intracranial self-stimulation; motivation; rat; selective
breeding; sweet preference
ID BRAIN; WITHDRAWAL; THRESHOLDS; TASTE; ESCALATION; PREFERENCE; NICOTINE;
SUCROSE; FACILITATION; CONSUMPTION
AB Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well-established model of drug-abuse vulnerability, with HiS rats being more likely to consume sweets and cocaine than LoS rats. Still, the nature of these differences is poorly understood. This study examined whether the motivational consequences of cocaine exposure are differentially expressed in HiS and LoS rats by measuring intracranial self-stimulation (ICSS) thresholds following acute injections of cocaine (10mg/kg). Reductions in ICSS thresholds following cocaine injection were greater in HiS rats than in LoS rats, suggesting that the reward-enhancing effects of cocaine are greater in the drug-vulnerable HiS than LoS rats. Higher cocaine-induced reward, indicated by lower ICSS thresholds, may explain the higher rates of drug consumption in sweet-preferring animal models, providing a clue to the etiology of cocaine addiction in vulnerable populations. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Radke, Anna K.; Zlebnik, Natalie E.; Holtz, Nathan A.; Carroll, Marilyn E.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
RP Radke, AK (reprint author), NIAAA, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM anna.radke@nih.gov
FU NIH [R01 DA003240-28]
FX The authors thank Dr Andrew Harris for advice on intracranial
self-stimulation and Seth Johnson for superb technical assistance. This
research was supported by NIH grant R01 DA003240-28 (M.E.C.).
NR 37
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD APR
PY 2016
VL 27
IS 2-3
SI SI
BP 133
EP 136
DI 10.1097/FBP.0000000000000182
PG 4
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA DK4MQ
UT WOS:000374892900005
PM 26292189
ER
PT J
AU Karev, GP
Kareva, I
AF Karev, G. P.
Kareva, I.
TI Mathematical Modeling of Extinction of Inhomogeneous Populations
SO BULLETIN OF MATHEMATICAL BIOLOGY
LA English
DT Article
DE Extinction of heterogeneous populations; Principle of minimal
information gain; Population extinction; Non-homogeneous models;
Frequency-dependent models; Minimum information loss; Internal time;
Time perception
ID TIME PERCEPTION; INFORMATION; DYNAMICS; DEATH
AB Mathematical models of population extinction have a variety of applications in such areas as ecology, paleontology and conservation biology. Here we propose and investigate two types of sub-exponential models of population extinction. Unlike the more traditional exponential models, the life duration of sub-exponential models is finite. In the first model, the population is assumed to be composed of clones that are independent from each other. In the second model, we assume that the size of the population as a whole decreases according to the sub-exponential equation. We then investigate the "unobserved heterogeneity," i.e., the underlying inhomogeneous population model, and calculate the distribution of frequencies of clones for both models. We show that the dynamics of frequencies in the first model is governed by the principle of minimum of Tsallis information loss. In the second model, the notion of "internal population time" is proposed; with respect to the internal time, the dynamics of frequencies is governed by the principle of minimum of Shannon information loss. The results of this analysis show that the principle of minimum of information loss is the underlying law for the evolution of a broad class of models of population extinction. Finally, we propose a possible application of this modeling framework to mechanisms underlying time perception.
C1 [Karev, G. P.] NIH, Natl Ctr Biotechnol Informat, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20892 USA.
[Kareva, I.] Floating Hosp Children, Tufts Med Ctr, Boston, MA 02111 USA.
[Kareva, I.] Arizona State Univ, Simon A Levin Math Computat & Modeling Sci Ctr, Engn Ctr A, Tempe, AZ 85287 USA.
RP Karev, GP (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20892 USA.
EM karev@ncbi.nlm.nih.gov; ikareva@asu.edu
FU Intramural Research Program of the NCBI, NIH
FX This research was partially supported by the Intramural Research Program
of the NCBI, NIH. The authors would also like to thank the anonymous
reviewers, whose comments and suggestions contributed to significant
improvement of the manuscript.
NR 32
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U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0092-8240
EI 1522-9602
J9 B MATH BIOL
JI Bull. Math. Biol.
PD APR
PY 2016
VL 78
IS 4
BP 834
EP 858
DI 10.1007/s11538-016-0166-0
PG 25
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA DL1UX
UT WOS:000375419200009
PM 27090117
ER
PT J
AU Zdanov, S
Mandapathil, M
Abu Eid, R
Adamson-Fadeyi, S
Wilson, W
Qian, JH
Carnie, A
Tarasova, N
Mkrtichyan, M
Berzofsky, JA
Whiteside, TL
Khleif, SN
AF Zdanov, Stephanie
Mandapathil, Magis
Abu Eid, Rasha
Adamson-Fadeyi, Saudat
Wilson, Willie
Qian, Jiahua
Carnie, Andrea
Tarasova, Nadya
Mkrtichyan, Mikayel
Berzofsky, Jay A.
Whiteside, Theresa L.
Khleif, Samir N.
TI Mutant KRAS Conversion of Conventional T Cells into Regulatory T Cells
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID K-RAS; SIGNALING PATHWAYS; TUMOR MICROENVIRONMENT; KINASE INHIBITORS;
EPITHELIAL-CELLS; TGF-BETA; C-JUN; MELANOMA; CANCER; ACTIVATION
AB Constitutive activation of the KRAS oncogene in human malignancies is associated with aggressive tumor growth and poor prognosis. Similar to other oncogenes, KRAS acts in a cell-intrinsic manner to affect tumor growth or survival. However, we describe here a different, cell-extrinsic mechanism through which mutant KRAS contributes to tumor development. Tumor cells carrying mutated KRAS induced highly suppressive T cells, and silencing KRAS reversed this effect. Overexpression of the mutant KRAS(G12V) gene in wild-type KRAS tumor cells led to regulatory T-cell (Treg) induction. We also demonstrate that mutant KRAS induces the secretion of IL10 and transforming growth factor-beta 1 (both required for Treg induction) by tumor cells through the activation of the MEK-ERK-AP1 pathway. Finally, we report that inhibition of KRAS reduces the infiltration of Tregs in KRAS-driven lung tumorigenesis even before tumor formation. This cell-extrinsic mechanism allows tumor cells harboring a mutant KRAS oncogene to escape immune recognition. Thus, an oncogene can promote tumor progression independent of its transforming activity by increasing the number and function of Tregs. This has a significant clinical potential, in which targeting KRAS and its downstream signaling pathways could be used as powerful immune modulators in cancer immunotherapy. (C) 2016 AACR.
C1 [Zdanov, Stephanie; Abu Eid, Rasha; Adamson-Fadeyi, Saudat; Qian, Jiahua; Carnie, Andrea; Mkrtichyan, Mikayel; Khleif, Samir N.] NCI, Canc Vaccine Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Mandapathil, Magis; Whiteside, Theresa L.] Univ Pittsburgh, Dept Pathol, IMPCL, Inst Canc, Pittsburgh, PA USA.
[Abu Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N.] Augusta Univ, Georgia Regents Univ, Georgia Canc Ctr, 1120 15th St,CN-2101A, Augusta, GA 30912 USA.
[Wilson, Willie] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Tarasova, Nadya] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD USA.
[Berzofsky, Jay A.] NIH, Mol Immunogenet & Vac Res Sect, Vaccine Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Adamson-Fadeyi, Saudat] Meharry Med Coll, Dept Canc Biol, Nashville, TN 37208 USA.
[Mandapathil, Magis] Univ Marburg, Dept Otorhinolaryngol, Marburg, Germany.
[Qian, Jiahua] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Mkrtichyan, Mikayel] FivePrime Therapeut, San Francisco, CA USA.
RP Khleif, SN (reprint author), Augusta Univ, Georgia Regents Univ, Georgia Canc Ctr, 1120 15th St,CN-2101A, Augusta, GA 30912 USA.
EM SKHLEIF@gru.edu
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (S.N.
Khleif).
NR 50
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U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD APR
PY 2016
VL 4
IS 4
BP 354
EP 365
DI 10.1158/2326-6066.CIR-15-0241
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA DL1RP
UT WOS:000375410000010
PM 26880715
ER
PT J
AU Contijoch, F
Rogers, K
Rears, H
Shahid, M
Kellman, P
Gorman, J
Gorman, RC
Yushkevich, P
Zado, ES
Supple, GE
Marchlinski, FE
Witschey, WRT
Han, Y
AF Contijoch, Francisco
Rogers, Kelly
Rears, Hannah
Shahid, Mohammed
Kellman, Peter
Gorman, Joseph, III
Gorman, Robert C.
Yushkevich, Paul
Zado, Erica S.
Supple, Gregory E.
Marchlinski, Francis E.
Witschey, Walter R. T.
Han, Yuchi
TI Quantification of Left Ventricular Function With Premature Ventricular
Complexes Reveals Variable Hemodynamics
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE cardiac arrhythmias; echocardiography; magnetic resonance imaging;
stroke volume; ventricular premature complexes
ID CONTRACTION-INDUCED CARDIOMYOPATHY; ATRIAL-FIBRILLATION; QRS DETECTION;
ANIMAL-MODEL; MRI; RECONSTRUCTION; ECTOPY; INTERVAL
AB Background Premature ventricular complexes (PVCs) are prevalent in the general population and are sometimes associated with reduced ventricular function. Current echocardiographic and cardiovascular magnetic resonance imaging techniques do not adequately address the effect of PVCs on left ventricular function.
Methods and Results Fifteen subjects with a history of frequent PVCs undergoing cardiovascular magnetic resonance imaging had real-time slice volume quantification performed using a 2-dimensional (2D) real-time cardiovascular magnetic resonance imaging technique. Synchronization of 2D real-time imaging with patient ECG allowed for different beats to be categorized by the loading beat RR duration and beat RR duration. For each beat type, global volumes were quantified via summation over all slices covering the entire ventricle. Different patterns of ectopy, including isolated PVCs, bigeminy, trigeminy, and interpolated PVCs, were observed. Global functional measurement of the different beat types based on timing demonstrated differences in preload, stroke volume, and ejection fraction. An average of hemodynamic function was quantified for each subject depending on the frequency of each observed beat type.
Conclusions Application of real-time cardiovascular magnetic resonance imaging in patients with PVCs revealed differential contribution of PVCs to hemodynamics.
C1 [Contijoch, Francisco] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Rogers, Kelly; Zado, Erica S.; Supple, Gregory E.; Marchlinski, Francis E.; Han, Yuchi] Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA.
[Rears, Hannah; Shahid, Mohammed; Yushkevich, Paul; Witschey, Walter R. T.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Gorman, Joseph, III; Gorman, Robert C.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
RP Han, Y (reprint author), Hosp Univ Penn, Div Cardiovasc, Room 9022,East Gates 3400 Spruce St, Philadelphia, PA 19104 USA.
EM yuchi.han@uphs.upenn.edu
FU National Institutes of Health [F31-HL120580, R00-HL108157, R01-EB014346,
R01-HL103723, R01-HL63954, T32-HL007954, T32-EB009384]; Cardiovascular
Medical Research and Education Fund (Philadelphia, PA)
FX This study was supported by grants from National Institutes of Health
(F31-HL120580, R00-HL108157, R01-EB014346, R01-HL103723, R01-HL63954,
T32-HL007954, and T32-EB009384) and Cardiovascular Medical Research and
Education Fund (Philadelphia, PA).
NR 31
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U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3149
EI 1941-3084
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD APR
PY 2016
VL 9
IS 4
AR e003520
DI 10.1161/CIRCEP.115.003520
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK3DK
UT WOS:000374796100005
PM 27009416
ER
PT J
AU Pashakhanloo, F
Herzka, DA
Ashikaga, H
Mori, S
Gai, N
Bluemke, DA
Trayanova, NA
McVeigh, ER
AF Pashakhanloo, Farhad
Herzka, Daniel A.
Ashikaga, Hiroshi
Mori, Susumu
Gai, Neville
Bluemke, David A.
Trayanova, Natalia A.
McVeigh, Elliot R.
TI Myofiber Architecture of the Human Atria as Revealed by Submillimeter
Diffusion Tensor Imaging
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE arrhythmias; cardiac; atrial function; atrial myoarchitecture; fiber
orientation; heart atria; diffusion tensor imaging; diffusion magnetic
resonance imaging
ID CANINE PULMONARY VEINS; STRUCTURAL COMPLEXITIES; RADIOFREQUENCY
ABLATION; HISTOLOGICAL VALIDATION; ELECTRICAL ACTIVATION;
FIBER-ORIENTATION; SPIN ECHOES; HUMAN HEART; FIBRILLATION; CONDUCTION
AB Background Accurate knowledge of the human atrial fibrous structure is paramount in understanding the mechanisms of atrial electric function in health and disease. Thus far, such knowledge has been acquired from destructive sectioning, and there is a paucity of data about atrial fiber architecture variability in the human population.
Methods and Results In this study, we have developed a customized 3-dimensional diffusion tensor magnetic resonance imaging sequence on a clinical scanner that makes it possible to image an entire intact human heart specimen ex vivo at submillimeter resolution. The data from 8 human atrial specimens obtained with this technique present complete maps of the fibrous organization of the human atria. The findings demonstrate that the main features of atrial anatomy are mostly preserved across subjects although the exact location and orientation of atrial bundles vary. Using the full tractography data, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Furthermore, quantitative characterization of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout different regions of the atria.
Conclusions The application of submillimeter diffusion tensor magnetic resonance imaging provides an unprecedented level of information on both human atrial structure, as well as its intersubject variability. The high resolution and fidelity of this data could enhance our understanding of structural contributions to atrial rhythm and pump disorders and lead to improvements in their targeted treatment.
C1 [Pashakhanloo, Farhad; Herzka, Daniel A.; Trayanova, Natalia A.; McVeigh, Elliot R.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
[Ashikaga, Hiroshi] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Mori, Susumu; McVeigh, Elliot R.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Gai, Neville; Bluemke, David A.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Med, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.
[McVeigh, Elliot R.] Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.
RP McVeigh, ER (reprint author), Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.; McVeigh, ER (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.; McVeigh, ER (reprint author), Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr MC0412, La Jolla, CA 92093 USA.
EM emcveigh@ucsd.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH) [DP1HL123271]; NIH
FX This study was supported by the National Institutes of Health (NIH)
Director's Pioneer Award to N.A. Trayanova (DP1HL123271) and the NIH
intramural research program.
NR 49
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U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3149
EI 1941-3084
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD APR
PY 2016
VL 9
IS 4
AR e004133
DI 10.1161/CIRCEP.116.004133
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK3DK
UT WOS:000374796100019
PM 27071829
ER
PT J
AU Rogers, T
Mahapatra, S
Kim, S
Eckhaus, MA
Schenke, WH
Mazal, JR
Campbell-Washburn, A
Sonmez, M
Faranesh, AZ
Ratnayaka, K
Lederman, RJ
AF Rogers, Toby
Mahapatra, Srijoy
Kim, Steven
Eckhaus, Michael A.
Schenke, William H.
Mazal, Jonathan R.
Campbell-Washburn, Adrienne
Sonmez, Merdim
Faranesh, Anthony Z.
Ratnayaka, Kanishka
Lederman, Robert J.
TI Transcatheter Myocardial Needle Chemoablation During Real-Time Magnetic
Resonance Imaging: A New Approach to Ablation Therapy for Rhythm
Disorders
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE cardiac electrophysiology; catheter ablation; electrophysiology;
magnetic resonance imaging; magnetic resonance imaging; interventional;
tachycardia; ventricular
ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; VENTRICULAR-TACHYCARDIA
ABLATION; CATHETER ABLATION; ATRIAL-FIBRILLATION; CHEMICAL ABLATION;
SCAR FORMATION; ETHANOL; ENHANCEMENT; ARRHYTHMIA; FEASIBILITY
AB Background Radiofrequency ablation for ventricular arrhythmias is limited by inability to visualize tissue destruction, by reversible conduction block resulting from edema surrounding lesions, and by insufficient lesion depth. We hypothesized that transcatheter needle injection of caustic agents doped with gadolinium contrast under real-time magnetic resonance imaging (MRI) could achieve deep, targeted, and irreversible myocardial ablation, which would be immediately visible.
Methods and Results Under real-time MRI guidance, ethanol or acetic acid was injected into the myocardium of 8 swine using MRI-conspicuous needle catheters. Chemoablation lesions had identical geometry by in vivo and ex vivo MRI and histopathology, both immediately and after 12 (7-17) days. Ethanol caused stellate lesions with patchy areas of normal myocardium, whereas acetic acid caused homogeneous circumscribed lesions of irreversible necrosis. Ischemic cardiomyopathy was created in 10 additional swine by subselective transcoronary ethanol administration into noncontiguous territories. After 12 (8-15) days, real-time MRI-guided chemoablationwith 2 to 5 injections to create a linear lesionsuccessfully eliminated the isthmus and local abnormal voltage activities.
Conclusions Real-time MRI-guided chemoablation with acetic acid enabled the intended arrhythmic substrate, whether deep or superficial, to be visualized immediately and ablated irreversibly. In an animal model of ischemic cardiomyopathy, obliteration of a conductive isthmus both anatomically and functionally and abolition of local abnormal voltage activities in areas of heterogeneous scar were feasible. This represents the first report of MRI-guided myocardial chemoablation, an approach that could improve the efficacy of arrhythmic substrate ablation in the thick ventricular myocardium.
C1 [Rogers, Toby; Schenke, William H.; Mazal, Jonathan R.; Campbell-Washburn, Adrienne; Sonmez, Merdim; Faranesh, Anthony Z.; Ratnayaka, Kanishka; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Eckhaus, Michael A.] NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA.
[Mahapatra, Srijoy] St Jude Med, Global Med Affairs, St Paul, MN USA.
[Kim, Steven] St Jude Med, Therapy Dev, St Paul, MN USA.
[Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA.
EM lederman@nih.gov
OI Rogers, Toby/0000-0002-6043-3137
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[Z01-HL005062]
FX This work was supported by the National Heart, Lung, and Blood
Institute, National Institutes of Health (Z01-HL005062).
NR 32
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U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3149
EI 1941-3084
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD APR
PY 2016
VL 9
IS 4
AR e003926
DI 10.1161/CIRCEP.115.003926
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK3DK
UT WOS:000374796100013
PM 27053637
ER
PT J
AU Fleg, JL
AF Fleg, Jerome L.
TI Healthy Lifestyle and Risk of Heart Failure: An Ounce of Prevention Well
Worth the Effort
SO CIRCULATION-HEART FAILURE
LA English
DT Editorial Material
DE Editorials; cardiovascular disease; heart failure; lifestyle;
prevention; risk factors
ID CARDIOVASCULAR-DISEASE PREVENTION; WOMEN; DIET; REDUCTION; STROKE;
ADULTS; MEN
C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8154, Bethesda, MD 20892 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8154, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 16
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD APR
PY 2016
VL 9
IS 4
AR e003155
DI 10.1161/CIRCHEARTFAILURE.116.003155
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK3DJ
UT WOS:000374796000015
PM 27072862
ER
PT J
AU Hsu, DC
Sereti, I
AF Hsu, Denise C.
Sereti, Irini
TI Serious Non-AIDS Events: Therapeutic Targets of Immune Activation and
Chronic Inflammation in HIV Infection
SO DRUGS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
T-CELL-ACTIVATION; C-REACTIVE PROTEIN; PLACEBO-CONTROLLED TRIAL;
CORONARY-HEART-DISEASE; INDIVIDUAL PARTICIPANT METAANALYSIS; SUSTAINED
VIROLOGICAL RESPONSE; TISSUE FACTOR EXPRESSION; HEPATITIS-C
AB In the antiretroviral therapy (ART) era, serious non-AIDS events (SNAEs) have become the major causes of morbidity and mortality in HIV-infected persons. Early ART initiation has the strongest evidence for reducing SNAEs and mortality. Biomarkers of immune activation, inflammation and coagulopathy do not fully normalize despite virologic suppression and persistent immune activation is an important contributor to SNAEs. A number of strategies aimed to reduce persistent immune activation including ART intensification to reduce residual viremia; treatment of co-infections to reduce chronic antigen stimulation; the use of anti-inflammatory agents, reducing microbial translocation as well as interventions to improve immune recovery through cytokine administration and reducing lymphoid tissue fibrosis, have been investigated. To date, there is little conclusive evidence on which strategies beyond treatment of hepatitis B and C co-infections and reducing cardiovascular risk factors will result in clinical benefits in patients already on ART with viral suppression. The use of statins seems to show early promise and larger clinical trials are underway to confirm their efficacy. At this stage, clinical care of HIV-infected patients should therefore focus on early diagnosis and prompt ART initiation, treatment of active co-infections and the aggressive management of co-morbidities until further data are available.
C1 [Hsu, Denise C.; Sereti, Irini] NIAID, NIH, Bg 10 Rm 11B07 10 Ctr Dr, Bethesda, MD 20814 USA.
RP Sereti, I (reprint author), NIAID, NIH, Bg 10 Rm 11B07 10 Ctr Dr, Bethesda, MD 20814 USA.
EM isereti@niaid.nih.gov
FU intramural research program of NIAID/NIH
FX The work of the authors was supported by the intramural research program
of NIAID/NIH. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 241
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U1 0
U2 0
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 0012-6667
EI 1179-1950
J9 DRUGS
JI Drugs
PD APR
PY 2016
VL 76
IS 5
BP 533
EP 549
DI 10.1007/s40265-016-0546-7
PG 17
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DK6RH
UT WOS:000375052300002
PM 26915027
ER
PT J
AU Ibrahim, M
Thearle, MS
Krakoff, J
Gluck, ME
AF Ibrahim, Mostafa
Thearle, Marie S.
Krakoff, Jonathan
Gluck, Marci E.
TI Perceived stress and anhedonia predict short-and long-term weight
change, respectively, in healthy adults
SO EATING BEHAVIORS
LA English
DT Article
DE Depression; Mood; Emotional eating; Longitudinal; Weight gain
ID EATING BEHAVIOR; DIETARY RESTRAINT; PHYSICAL-ACTIVITY; FOOD-INTAKE;
OBESITY; DEPRESSION; DISINHIBITION; OVERWEIGHT; APPETITE; DISEASE
AB Objective: Perceived stress; emotional eating; anhedonia; depression and dietary restraint, hunger, and disinhibition have been studied as risk factors for obesity. However, the majority of studies have been cross-sectional and the directionality of these relationships remains unclear. In this longitudinal study, we assess their impact on future weight change.
Methods: Psychological predictors of weight change in short- (6 month) and long-term (>1 year) periods were studied in 65 lean and obese individuals in two cohorts. Subjects participated in studies of food intake and metabolism that did not include any type of medication or weight loss interventions. They completed psychological questionnaires at baseline and weight change was monitored at follow-up visits.
Results: At six months, perceived stress predicted weight gain (r(2) = 0.23, P = 0.02). There was a significant interaction (r(2) = .38, P = 0.009) between perceived stress and positive emotional eating, such that higher scores in both predicted greater weight gain, while those with low stress but high emotional eating scores lost weight. For long-term, higher anhedonia scores predicted weight gain (r(2) = 0.24, P = 0.04). Depression moderated these effects such that higher scores in both predicted weight gain but higher depression and lower anhedonia scores predicted weight loss.
Conclusion: There are different behavioral determinants for short-and long-term weight change. Targeting perceived stress may help with short-term weight loss while depression and anhedonia may be better targets for long-term weight regulation. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Ibrahim, Mostafa; Thearle, Marie S.; Krakoff, Jonathan; Gluck, Marci E.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA.
RP Ibrahim, M (reprint author), 4212 N 16th St, Phoenix, AZ 85016 USA.
EM mostafa928@gmail.com
FU NIH/NIDDK
FX MI and MST collected and analyzed data. All authors had equal
involvement in writing the manuscript and reviewing submitted version.
This research was supported by the Intramural Research Program of the
NIH/NIDDK (Clinical trial IDs are NCT00523627, NCT00342732).
NR 48
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Z9 0
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1471-0153
EI 1873-7358
J9 EAT BEHAV
JI Eat. Behav.
PD APR
PY 2016
VL 21
BP 214
EP 219
DI 10.1016/j.eatbeh.2016.03.009
PG 6
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DK7XQ
UT WOS:000375140600037
PM 27002703
ER
PT J
AU Semba, RD
Shardell, M
Ashour, FAS
Moaddel, R
Trehan, I
Maleta, KM
Ordiz, MI
Kraemer, K
Khadeer, MA
Ferrucci, L
Manary, MJ
AF Semba, Richard D.
Shardell, Michelle
Ashour, Fayrouz A. Sakr
Moaddel, Ruin
Trehan, Indi
Maleta, Kenneth M.
Ordiz, M. Isabel
Kraemer, Klaus
Khadeer, Mohammed A.
Ferrucci, Luigi
Manary, Mark J.
TI Child Stunting is Associated with Low Circulating Essential Amino Acids
SO EBIOMEDICINE
LA English
DT Article
DE Amino acids; Children; Glycerophospholipids; Malnutrition;
Sphingolipids; Stunting
ID RANDOMIZED CONTROLLED-TRIAL; CHOLINE KINASE BETA; GROWTH; HEALTH;
NUTRIENT; PHOSPHATIDYLCHOLINE; SUPPLEMENTATION; METABOLISM; MECHANISMS;
NUTRITION
AB Background: Stunting affects about one-quarter of children under five worldwide. The pathogenesis of stunting is poorly understood. Nutritional interventions have had only modest effects in reducing stunting. We hypothesized that insufficiency in essential amino acids may be limiting the linear growth of children.
Methods: We used a targeted metabolomics approach to measure serum amino acids, glycerophospholipids, sphingolipids, and other metabolites using liquid chromatography-tandem mass spectrometry in 313 children, aged 12-59 months, from rural Malawi. Children underwent anthropometry.
Findings: Sixty-two percent of the children were stunted. Children with stunting had lower serum concentrations of all nine essential amino acids (tryptophan, isoleucine, leucine, valine, methionine, threonine, histidine, phenylalanine, lysine) compared with nonstunted children (p < 0.01). In addition, stunted children had significantly lower serum concentrations of conditionally essential amino acids (arginine, glycine, glutamine), non-essential amino acids (asparagine, glutamate, serine), and six different sphingolipids compared with nonstunted children. Stunting was also associated with alterations in serum glycerophospholipid concentrations.
Interpretation: Our findings support the idea that children with a high risk of stunting may not be receiving an adequate dietary intake of essential amino acids and choline, an essential nutrient for the synthesis of sphingolipids and glycerophospholipids. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Shardell, Michelle; Moaddel, Ruin; Khadeer, Mohammed A.; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Ashour, Fayrouz A. Sakr] Univ Maryland, Coll Agr & Nat Resources, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Trehan, Indi; Ordiz, M. Isabel; Manary, Mark J.] Washington Univ, Dept Pediat, St Louis, MO 63130 USA.
[Trehan, Indi; Maleta, Kenneth M.; Manary, Mark J.] Univ Malawi, Coll Med, Sch Publ Hlth & Family Med, Blantyre, Malawi.
[Kraemer, Klaus] Sight & Life, Basel, Switzerland.
[Kraemer, Klaus] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
RP Semba, RD (reprint author), Smith Bldg M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
OI Maleta, Ken/0000-0002-2536-3938
FU NEI NIH HHS [R01 EY024596]; NIA NIH HHS [R01 AG027012]
NR 38
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U1 4
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD APR
PY 2016
VL 6
BP 246
EP 252
DI 10.1016/j.ebiom.2016.02.030
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DK7BS
UT WOS:000375080400038
PM 27211567
ER
PT J
AU Buhnerkempe, MG
Webb, CT
Merton, AA
Buhnerkempe, JE
Givens, GH
Miller, RS
Hoeting, JA
AF Buhnerkempe, Michael G.
Webb, Colleen T.
Merton, Andrew A.
Buhnerkempe, John E.
Givens, Geof H.
Miller, Ryan S.
Hoeting, Jennifer A.
TI Identification of migratory bird flyways in North America using
community detection on biological networks
SO ECOLOGICAL APPLICATIONS
LA English
DT Article
DE Anas acuta; Anas carolinensis; Anas platyrhnchos; Branta canadensis;
community detection; consolidation factor; flyways; migration; network;
waterfowl
ID ADAPTIVE MANAGEMENT; WATERFOWL HARVESTS; HUMAN INFECTION; INFLUENZA;
ORIGIN; VIRUS; UNCERTAINTY; MOVEMENTS; HABITAT; PRAIRIE
AB Migratory behavior of waterfowl populations in North America has traditionally been broadly characterized by four north-south flyways, and these flyways have been central to the management of waterfowl populations for more than 80 yr. However, previous flyway characterizations are not easily updated with current bird movement data and fail to provide assessments of the importance of specific geographical regions to the identification of flyways. Here, we developed a network model of migratory movement for four waterfowl species, Mallard (Anas platyrhnchos), Northern Pintail (A. acuta), American Green-winged Teal (A. carolinensis), and Canada Goose (Branta canadensis), in North America, using bird band and recovery data. We then identified migratory flyways using a community detection algorithm and characterized the importance of smaller geographic regions in identifying flyways using a novel metric, the consolidation factor. We identified four main flyways for Mallards, Northern Pintails, and American Green-winged Teal, with the flyway identification in Canada Geese exhibiting higher complexity. For Mallards, flyways were relatively consistent through time. However, consolidation factors revealed that for Mallards and Green-winged Teal, the presumptive Mississippi flyway was potentially a zone of high mixing between other flyways. Our results demonstrate that the network approach provides a robust method for flyway identification that is widely applicable given the relatively minimal data requirements and is easily updated with future movement data to reflect changes in flyway definitions and management goals.
C1 [Buhnerkempe, Michael G.; Merton, Andrew A.; Givens, Geof H.; Hoeting, Jennifer A.] Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA.
[Buhnerkempe, Michael G.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
[Buhnerkempe, Michael G.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Buhnerkempe, Michael G.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Buhnerkempe, John E.] Illinois Dept Nat Resources, Div Wildlife Resources, Springfield, IL 62702 USA.
[Miller, Ryan S.] USDA, Anim & Plant Hlth Inspect Serv, Ctr Epidemiol, Ft Collins, CO 80521 USA.
[Miller, Ryan S.] USDA, Anim & Plant Hlth Inspect Serv, Ctr Anim Hlth, Ft Collins, CO 80521 USA.
[Givens, Geof H.] Givens Stat Solut LLC, Ft Collins, CO 80526 USA.
RP Buhnerkempe, MG (reprint author), Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA.; Buhnerkempe, MG (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.; Buhnerkempe, MG (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.; Buhnerkempe, MG (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM michael.buhnerkempe@gmail.com
OI Miller, Ryan/0000-0003-3892-0251
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; USDA
[07-7100-0228-CA9, 09-7100-0305-CA, 11-9208-0269-CA, 09-9208-0235-CA]
FX M. G. Buhnerkempe and C. T. Webb acknowledge funding from the Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, Department of Homeland Security, and
Fogarty International Center, National Institutes of Health. Funding for
this work was also provided by USDA Cooperative Agreements
07-7100-0228-CA9, 09-7100-0305-CA, 11-9208-0269-CA and 09-9208-0235-CA.
We would like to thank Shweta Bansal, Dan Grear, and Clint Leach for
useful discussions on conceptual and methodological issues related to
network analyses.
NR 42
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U1 10
U2 25
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1051-0761
EI 1939-5582
J9 ECOL APPL
JI Ecol. Appl.
PD APR
PY 2016
VL 26
IS 3
BP 740
EP 751
DI 10.1890/15-0934
PG 12
WC Ecology; Environmental Sciences
SC Environmental Sciences & Ecology
GA DK3TO
UT WOS:000374840500008
PM 27411247
ER
PT J
AU Weidemann, E
Andersson, PL
Bidleman, T
Boman, C
Carlin, DJ
Collina, E
Cormier, SA
Gouveia-Figueira, SC
Gullett, BK
Johansson, C
Lucas, D
Lundin, L
Lundstedt, S
Marklund, S
Nording, ML
Ortuno, N
Sallam, AA
Schmidt, FM
Jansson, S
AF Weidemann, Eva
Andersson, Patrik L.
Bidleman, Terry
Boman, Christoffer
Carlin, Danielle J.
Collina, Elena
Cormier, Stephania A.
Gouveia-Figueira, Sandra C.
Gullett, Brian K.
Johansson, Christer
Lucas, Donald
Lundin, Lisa
Lundstedt, Staffan
Marklund, Stellan
Nording, Malin L.
Ortuno, Nuria
Sallam, Asmaa A.
Schmidt, Florian M.
Jansson, Stina
TI 14th congress of combustion by-products and their health effects-origin,
fate, and health effects of combustion-related air pollutants in the
coming era of bio-based energy sources
SO ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
LA English
DT Article
DE Products of incomplete combustion; Human health; Soot; Particles;
Polychlorinated dibenzo-p-dioxins; Polychlorinated dibenzofurans;
Congress paper
ID MASS-SPECTROMETRY; VIRUS-INFECTION; FLUE-GAS; WASTE; PYROLYSIS;
DECOMPOSITION; EMISSION; LIGNINS; DIOXINS; CARBON
AB The 14th International Congress on Combustion By-Products and Their Health Effects was held in UmeAyen, Sweden from June 14th to 17th, 2015. The Congress, mainly sponsored by the National Institute of Environmental Health Sciences Superfund Research Program and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, focused on the "Origin, fate and health effects of combustion-related air pollutants in the coming era of bio-based energy sources". The international delegates included academic and government researchers, engineers, scientists, policymakers and representatives of industrial partners. The Congress provided a unique forum for the discussion of scientific advances in this research area since it addressed in combination the health-related issues and the environmental implications of combustion by-products. The scientific outcomes of the Congress included the consensus opinions that: (a) there is a correlation between human exposure to particulate matter and increased cardiac and respiratory morbidity and mortality; (b) because currently available data does not support the assessment of differences in health outcomes between biomass smoke and other particulates in outdoor air, the potential human health and environmental impacts of emerging air-pollution sources must be addressed. Assessment will require the development of new approaches to characterize combustion emissions through advanced sampling and analytical methods. The Congress also concluded the need for better and more sustainable e-waste management and improved policies, usage and disposal methods for materials containing flame retardants.
C1 [Weidemann, Eva; Andersson, Patrik L.; Bidleman, Terry; Gouveia-Figueira, Sandra C.; Lundin, Lisa; Lundstedt, Staffan; Nording, Malin L.; Jansson, Stina] Umea Univ, Dept Chem, Umea, Sweden.
[Boman, Christoffer; Schmidt, Florian M.] Umea Univ, Dept Appl Phys & Elect, Thermochem Energy Convers Lab, Umea, Sweden.
[Carlin, Danielle J.] NIEHS, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Collina, Elena] Univ Milano Bicocca, Dept Earth & Environm Sci, Milan, Italy.
[Cormier, Stephania A.; Sallam, Asmaa A.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA.
[Cormier, Stephania A.; Sallam, Asmaa A.] Le Bonheur Childrens Hosp, Childrens Fdn Res Inst, Memphis, TN USA.
[Gullett, Brian K.] US EPA, Off Res & Dev, Natl Risk Management Res Lab, Res Triangle Pk, NC 27711 USA.
[Johansson, Christer] Stockholm Univ, Dept Environm Sci & Analyt Chem, S-10691 Stockholm, Sweden.
[Johansson, Christer] Environm & Hlth Adm, Stockholm, Sweden.
[Lucas, Donald] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
[Marklund, Stellan] Umea Univ, Bio4Energy, Umea, Sweden.
[Ortuno, Nuria] Univ Alicante, Dept Chem Engn, E-03080 Alicante, Spain.
RP Weidemann, E (reprint author), Umea Univ, Dept Chem, Umea, Sweden.
EM eva.weidemann@umu.se
RI Ortuno Garcia, Nuria/E-7127-2017;
OI Ortuno Garcia, Nuria/0000-0003-0442-4890; Nording,
Malin/0000-0002-1732-8147; Weidemann, Eva/0000-0001-5415-9330
FU National Institutes of Environmental Health Sciences; Swedish Research
Council for Environment, Agricultural Sciences and Spatial
Planning-Formas [219-2014-291]
FX The 14th Combustion By-Products and Their Health Effects Congress was
supported by funds from National Institutes of Environmental Health
Sciences to SC, and the Swedish Research Council for Environment,
Agricultural Sciences and Spatial Planning-Formas (219-2014-291) to SJ,
CB, MLN, LL, and EW.
NR 23
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U1 9
U2 19
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0944-1344
EI 1614-7499
J9 ENVIRON SCI POLLUT R
JI Environ. Sci. Pollut. Res.
PD APR
PY 2016
VL 23
IS 8
BP 8141
EP 8159
DI 10.1007/s11356-016-6308-y
PG 19
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DK5XN
UT WOS:000374994600105
PM 26906006
ER
PT J
AU Ferrington, DA
Kapphahn, RJ
Leary, MM
Atilano, SR
Terluk, MR
Karunadharma, P
Chen, GKJ
Ratnapriya, R
Swaroop, A
Montezuma, SR
Kenney, MC
AF Ferrington, Deborah A.
Kapphahn, Rebecca J.
Leary, Michaela M.
Atilano, Shari R.
Terluk, Marcia R.
Karunadharma, Pabalu
Chen, George Kuei-Jie
Ratnapriya, Rinki
Swaroop, Anand
Montezuma, Sandra R.
Kenney, M. Cristina
TI Increased retinal mtDNA damage in the CFH variant associated with
age-related macular degeneration
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Complement factor H; Eyebank tissue;
Mitochondria; mtDNA; Haplogroups; Inflammation
ID COMPLEMENT FACTOR-H; MITOCHONDRIAL-DNA HAPLOGROUPS; PIGMENT
EPITHELIAL-CELLS; DISEASE-ASSOCIATED FORM; C-REACTIVE PROTEIN;
PROGRESSIVE STAGES; OXIDATIVE STRESS; BRUCHS MEMBRANE; ACTIVATION;
BINDING
AB Age-related macular degeneration (AMD) is a major cause of blindness among the elderly in the developed world. Genetic analysis of AMD has identified 34 high-risk loci associated with AMD. The genes at these high risk loci belong to diverse biological pathways, suggesting different mechanisms leading to AMD pathogenesis. Thus, therapies targeting a single pathway for all AMD patients will likely not be universally effective. Recent evidence suggests defects in mitochondria (mt) of the retinal pigment epithelium (RPE) may constitute a key pathogenic event in some AMD patients. The purpose of this study is to determine if individuals with a specific genetic background have a greater propensity for mtDNA damage. We used human eyebank tissues from 76 donors with AMD and 42 age-matched controls to determine the extent of mtDNA damage in the RPE that was harvested from the macula using a long extension polymerase chain reaction assay. Genotype analyses were performed for ten common AMD-associated nuclear risk alleles (ARMS2, TNFRSF10A, CFH, C2, C3, APOE, CETP, LIPC, VEGF and COL10A1) and mtDNA haplogroups. Sufficient samples were available for genotype association with mtDNA damage for TNFRSF10A, CFH, CETP, VEGFA, and COL10A1. Our results show that AMD donors carrying the high risk allele for CFH (C) had significantly more mtDNA damage compared with donors having the wild-type genetic profile. The data from an additional 39 donors (12 controls and 27 AMD) genotyped for CFH alleles further supported these findings. Taken together, these studies provide the rationale for a more personalized approach for treating AMD by uncovering a significant correlation between the CFH high risk allele and accelerated mtDNA damage. Patients harboring this genetic risk factor may benefit from therapies that stabilize and protect the mt in the RPE. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Ferrington, Deborah A.; Kapphahn, Rebecca J.; Leary, Michaela M.; Terluk, Marcia R.; Karunadharma, Pabalu; Montezuma, Sandra R.] Univ Minnesota, Dept Ophthalmol & Visual Neurosci, Minneapolis, MN 55455 USA.
[Atilano, Shari R.; Chen, George Kuei-Jie; Kenney, M. Cristina] Univ Calif Irvine, Gavin Herbert Eye Inst, Irvine, CA 92697 USA.
[Ratnapriya, Rinki; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
RP Ferrington, DA (reprint author), 380 Lions Res Bldg,2001 6th St SE, Minneapolis, MN 55455 USA.
EM ferri013@umn.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU Elaine and Robert Larson Endowed Vision Research Chair; Beckman
Initiative for Macular Research [1004, 1303]; Foundation Fighting
Blindness [TA-NMT-0613-0620-UMN]; National Institutes of Health
[T32-AG29796]; Discovery Eye Foundation; Polly and Michael Smith
Foundation; National Eye Institute Intramural Research Program; Research
to Prevent Blindness
FX This work was supported by the Elaine and Robert Larson Endowed Vision
Research Chair (to DAF); Beckman Initiative for Macular Research (#1004,
#1303 to DAF); Foundation Fighting Blindness (TA-NMT-0613-0620-UMN to
DAF); An Anonymous Donor for Macular Degeneration Research and an
unrestricted grant from Research to Prevent Blindness to the Department
of Ophthalmology and Visual Neurosciences; National Institutes of Health
(T32-AG29796 to MRT); Discovery Eye Foundation (to MCK); Polly and
Michael Smith Foundation (to MCK) and the National Eye Institute
Intramural Research Program (to AS).
NR 47
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Z9 2
U1 1
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD APR
PY 2016
VL 145
BP 269
EP 277
DI 10.1016/j.exer.2016.01.018
PG 9
WC Ophthalmology
SC Ophthalmology
GA DL1DL
UT WOS:000375372300030
PM 26854823
ER
PT J
AU Boyle, EB
Viet, SM
Wright, DJ
Merrill, LS
Alwis, KU
Blount, BC
Mortensen, ME
Moye, J
Dellarco, M
AF Boyle, Elizabeth Barksdale
Viet, Susan M.
Wright, David J.
Merrill, Lori S.
Alwis, K. Udeni
Blount, Benjamin C.
Mortensen, Mary E.
Moye, John, Jr.
Dellarco, Michael
TI Assessment of Exposure to VOCs among Pregnant Women in the National
Children's Study
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE birth cohort study; pregnant women; tobacco; volatile organic compounds;
urinary metabolites; National Children's Study
ID VOLATILE ORGANIC-COMPOUNDS; TANDEM MASS-SPECTROMETRY; URINARY
METABOLITES; SERUM COTININE; NONSMOKERS; BENZENE; SMOKERS;
DISTRIBUTIONS; DETERMINANTS; BIOMARKERS
AB Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children's Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N-acetyl-S-(benzyl)-L-cysteine (BMA), and paint use was positively associated with the xylene metabolites 2-methylhippuric acid (2MHA) and 3-Methylhippuric acid & 4-methylhippuric acid (3MHA + 4MHA). A near-significant (p = 0.06) relationship was observed between acrylamide metabolites and observation of incense.
C1 [Boyle, Elizabeth Barksdale; Viet, Susan M.; Wright, David J.; Merrill, Lori S.] Westat Corp, Hlth Studies, 1600 Res Blvd, Rockville, MD 20850 USA.
[Alwis, K. Udeni; Blount, Benjamin C.] Ctr Dis Control & Prevent, Div Sci Lab, Tobacco & Volatiles Branch, Atlanta, GA 30341 USA.
[Mortensen, Mary E.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA.
[Moye, John, Jr.; Dellarco, Michael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Boyle, EB (reprint author), Westat Corp, Hlth Studies, 1600 Res Blvd, Rockville, MD 20850 USA.
EM eboyle@nas.edu; SusanViet@westat.com; DavidWright@Westat.com;
LoriMerrill@westat.com; eoe3@cdc.gov; bkb3@cdc.gov; zeo4@cdc.gov;
moyej@exchange.nih.go; dellarcom@mail.nih.gov
OI Boyle, Elizabeth/0000-0002-9412-7998
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); Office of the Director of the National Institutes
of Health; NICHD [HHSN275201200120U/GS-234-8144H]
FX This manuscript, a "primary NCS publication", was developed by a writing
team assembled by the NCS Publications Committee for the purpose of
sharing centrally collected NCS data. The analysis was conducted as part
of the National Children's Study, supported by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), and funded, through its appropriation, by the Office of the
Director of the National Institutes of Health. Supported in part by
NICHD Contract No. HHSN275201200120U/GS-234-8144H. The authors thank the
participants of the National Children's Study and the study
investigators and study center staff.
NR 42
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U1 4
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD APR
PY 2016
VL 13
IS 4
AR 376
DI 10.3390/ijerph13040376
PG 16
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA DK9DR
UT WOS:000375231300024
PM 27043585
ER
PT J
AU Gorai, AK
Tchounwou, PB
Tuluri, F
AF Gorai, Amit Kr.
Tchounwou, Paul B.
Tuluri, Francis
TI Association between Ambient Air Pollution and Asthma Prevalence in
Different Population Groups Residing in Eastern Texas, USA
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE air pollution; asthma; age; gender; race; Texas; USA
ID EMERGENCY-DEPARTMENT VISITS; LONG-TERM EXPOSURE; GEOGRAPHIC
INFORMATION-SYSTEMS; TIME-SERIES ANALYSIS; NEW-YORK-CITY; DAILY
MORTALITY; PARTICULATE MATTER; HOSPITAL ADMISSIONS; CARDIOVASCULAR
MORTALITY; SPATIAL-ANALYSIS
AB Air pollution has been an on-going research focus due to its detrimental impact on human health. However, its specific effects on asthma prevalence in different age groups, genders and races are not well understood. Thus, the present study was designed to examine the association between selected air pollutants and asthma prevalence in different population groups during 2010 in the eastern part of Texas, USA. The pollutants considered were particulate matter (PM2.5 with an aerodynamic diameter less than 2.5 micrometers) and surface ozone. The population groups were categorized based on age, gender, and race. County-wise asthma hospital discharge data for different age, gender, and racial groups were obtained from Texas Asthma Control Program, Office of Surveillance, Evaluation and Research, Texas Department of State Health Services. The annual means of the air pollutants were obtained from the United States Environmental Protection Agency (U.S. EPA)'s air quality system data mart program. Pearson correlation analyzes were conducted to examine the relationship between the annual mean concentrations of pollutants and asthma discharge rates (ADR) for different age groups, genders, and races. The results reveal that there is no significant association or relationship between ADR and exposure of air pollutants (PM2.5, and O-3). The study results showed a positive correlation between PM2.5 and ADR and a negative correlation between ADR and ozone in most of the cases. These correlations were not statistically significant, and can be better explained by considering the local weather conditions. The research findings facilitate identification of hotspots for controlling the most affected populations from further environmental exposure to air pollution, and for preventing or reducing the health impacts.
C1 [Gorai, Amit Kr.] Natl Inst Technol, Dept Min Engn, Rourkela 769008, Odisha, India.
[Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIMHD RCMI Ctr Environm Hlth, NIH, Jackson, MS 39217 USA.
[Tuluri, Francis] Jackson State Univ, Dept Ind Syst & Technol, Jackson, MS 39217 USA.
RP Gorai, AK (reprint author), Natl Inst Technol, Dept Min Engn, Rourkela 769008, Odisha, India.; Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIMHD RCMI Ctr Environm Hlth, NIH, Jackson, MS 39217 USA.
EM amit_gorai@yahoo.co.uk; paul.b.tchounwou@jsums.edu;
francis.tuluri@jsums.edu
FU Department of Science and Technology, New Delhi [SR/FTP/17/2012];
National Institutes of Health (NIMHD-RCMI) [G12MD007581]
FX Authors are thankful to U.S. EPA for providing the air pollution data
available on the website for public use, and to Texas Department of
State Health Services for providing the quarterly county wise asthma
data. The supports from the Department of Science and Technology, New
Delhi Grant No. SR/FTP/17/2012 and National Institutes of Health
(NIMHD-RCMI Grant No. G12MD007581) are also acknowledged.
NR 88
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U1 7
U2 17
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD APR
PY 2016
VL 13
IS 4
AR 378
DI 10.3390/ijerph13040378
PG 17
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA DK9DR
UT WOS:000375231300026
PM 27043587
ER
PT J
AU Patlolla, AK
Randolph, J
Kumari, SA
Tchounwou, PB
AF Patlolla, Anita K.
Randolph, Jonathan
Kumari, S. Anitha
Tchounwou, Paul B.
TI Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE graphene oxide; serum creatine; blood urea nitrogen; catalase;
glutathione peroxidase; superoxide dismutase; lipid hydroperoxide;
Sprague-Dawley rats
ID OXIDATIVE STRESS; CARBON NANOTUBES; MICE; EFFICIENCY; BACTERIA; DELIVERY
AB Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO) in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications.
C1 [Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, NIH, Jackson, MS 39217 USA.
[Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA.
[Randolph, Jonathan] Jackson State Univ, CESTEME Program Teacher, Jackson Publ Sch, Jackson, MS 39217 USA.
[Kumari, S. Anitha] Osmania Univ, Coll Women, Hyderabad 500001, Andhra Pradesh, India.
RP Patlolla, AK (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, NIH, Jackson, MS 39217 USA.; Patlolla, AK (reprint author), Jackson State Univ, Dept Biol, Jackson, MS 39217 USA.
EM anita.k.patlolla@jsums.edu; mustang4762@gmail.com;
anitha_shinde2001@yahoo.com; paul.b.tchounwou@jsums.edu
FU U.S. Department of Defense [W911NF-11-1-0123]; National Institutes of
Health [G12MD007581]
FX This research was made possible by CESTEME (Grant # W911NF-11-1-0123)
funded by the U.S. Department of Defense and by RCMI (Grant #
G12MD007581) funded by the National Institutes of Health.
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U1 0
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD APR
PY 2016
VL 13
IS 4
AR 380
DI 10.3390/ijerph13040380
PG 15
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA DK9DR
UT WOS:000375231300028
PM 27043588
ER
PT J
AU Adams, JW
Watts, DH
Phelps, BR
AF Adams, Joella W.
Watts, D. Heather
Phelps, B. Ryan
TI A systematic review of the effect of HIV infection and antiretroviral
therapy on the risk of pre-eclampsia
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Review
DE Antiretroviral therapy; HIV/AIDS; HIV in women; Pre-eclampsia
ID PREGNANT-WOMEN; ECLAMPSIA; HIV/AIDS; OUTCOMES
AB Background: The associations between HIV infection, antiretroviral therapy (ART), and pre-eclampsia are unclear. Objectives: To summarize research and clarify the implications of HIV and ART on pre-eclampsia risk. Search strategy: MedLine, PubMed, Web of Science, and the Cochrane Library were searched for studies published between 2003 and July 2014, using relevant keywords. Selection criteria: Full-text review was dependent on the inclusion of pre-eclampsia as an outcome and original data. Data collection and analysis: Data for population, confounders, limitations, and measures of association were qualitatively assessed. Main results: Among 550 records identified, 70 were screened, and 13 were included. Five of the nine studies comparing pre-eclampsia risk between women with and without HIV infection found no significant difference; only one found that women living with HIV were more likely to experience pre-eclampsia. Two studies found that women living with HIV who were receiving ART at conception were more likely to experience pre-eclampsia than were those not receiving ART at conception. Two studies reported that pre-eclampsia rates did not differ by ART regimen. Conclusions: There is insufficient evidence to conclude that women living with HIV and receiving ART have a higher risk of pre-eclampsia than do women without HIV infection; further research is needed to assess the association between ART and pre-eclampsia. (C) 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Adams, Joella W.; Phelps, B. Ryan] US Agcy Int Dev, Washington, DC 20523 USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
RP Adams, JW (reprint author), Bur Global Hlth, Global Hlth Fellows Program 2, USAID Off HIV AIDS, 2100 Crystal Dr,9040A, Arlington, VA 22202 USA.
EM joella_adams@brown.edu
OI Adams, Joella/0000-0002-7703-5944
NR 24
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U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
EI 1879-3479
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD APR
PY 2016
VL 133
IS 1
BP 17
EP 21
DI 10.1016/j.ijgo.2015.08.007
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DJ7CT
UT WOS:000374370200004
PM 26797203
ER
PT J
AU Ayres-de-Campos, D
Spong, CY
Chandraharan, E
AF Ayres-de-Campos, Diogo
Spong, Catherine Y.
Chandraharan, Edwin
CA FIGO Intrapartum Fetal Monitoring
TI FIGO consensus guidelines on intrapartum fetal monitoring:
Cardiotocography (vol 131, pg 13, 2015)
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Correction
C1 [Ayres-de-Campos, Diogo] Univ Porto, S Joao Hosp, Inst Biomed Engn, Sch Med, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Chandraharan, Edwin] St Georges Univ Hosp NHS Fdn Trust, London, England.
RP Ayres-de-Campos, D (reprint author), Univ Porto, S Joao Hosp, Inst Biomed Engn, Sch Med, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
EI 1879-3479
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD APR
PY 2016
VL 133
IS 1
BP 130
EP 130
DI 10.1016/j.ijgo.2016.02.005
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DJ7CT
UT WOS:000374370200031
ER
PT J
AU Inamura, K
Song, MY
Jung, S
Nishihara, R
Yamauchi, M
Lochhead, P
Qian, ZR
Kim, SA
Mima, K
Sukawa, Y
Masuda, A
Imamura, Y
Zhang, XH
Pollak, MN
Mantzoros, CS
Harris, CC
Giovannucci, E
Fuchs, CS
Cho, E
Chan, AT
Wu, KN
Ogino, S
AF Inamura, Kentaro
Song, Mingyang
Jung, Seungyoun
Nishihara, Reiko
Yamauchi, Mai
Lochhead, Paul
Qian, Zhi Rong
Kim, Sun A.
Mima, Kosuke
Sukawa, Yasutaka
Masuda, Atsuhiro
Imamura, Yu
Zhang, Xuehong
Pollak, Michael N.
Mantzoros, Christos S.
Harris, Curtis C.
Giovannucci, Edward
Fuchs, Charles S.
Cho, Eunyoung
Chan, Andrew T.
Wu, Kana
Ogino, Shuji
TI Prediagnosis Plasma Adiponectin in Relation to Colorectal Cancer Risk
According to KRAS Mutation Status
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; LIFE-STYLE FACTORS; KI-RAS
MUTATIONS; PIK3CA MUTATION; WEIGHT ADIPONECTIN; INSULIN-RESISTANCE;
PHYSICAL-ACTIVITY; PROGNOSTIC ROLE; ASSOCIATIONS; PREVENTION
AB Background: Low levels of adiponectin (ADIPOQ; HGNC ID; HGNC: 13633), an adipokine, are associated with obesity, adiposity, excess energy balance, and increased risk of colorectal neoplasia. Given the reported association of increased body mass index (BMI) and low-level physical activity with KRAS-mutated colorectal tumor, we hypothesized that low-level plasma adiponectin might be associated with increased risk of KRAS-mutant colorectal carcinoma but not with risk of KRAS wild-type carcinoma.
Methods: We conducted molecular pathological epidemiology research using a nested case-control study design (307 incident rectal and colon cancer case patients and 593 matched control individuals) within prospective cohort studies, the Nurses' Health Study (152 case patients and 297 control individuals, with blood collection in 1989-1990) and the Health Professionals Follow-up Study (155 case patients and 296 control individuals, with blood collection in 1993-1995). Multivariable conditional logistic regression models and two-sided likelihood ratio tests were used to assess etiologic heterogeneity of the associations.
Results: The association of low-level plasma adiponectin with colorectal cancer risk statistically significantly differed by KRAS mutation status (P-heterogeneity = .004). Low levels of plasma adiponectin were associated with KRAS-mutant colorectal cancer (for the lowest vs highest tertile: multivariable odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.50 to 5.34, P-trend = .002) but not with KRAS wild-type cancer (for the lowest vs highest tertile: multivariable OR = 0.83, 95% CI = 0.49 to 1.43, P-trend = .48). In secondary analyses, the association between plasma adiponectin and colorectal cancer did not appreciably differ by BRAF or PIK3CA oncogene mutation status.
Conclusions: Low-level plasma adiponectin is associated with KRAS-mutant colorectal cancer risk but not with KRAS wildtype cancer risk.
C1 [Inamura, Kentaro; Nishihara, Reiko; Yamauchi, Mai; Lochhead, Paul; Qian, Zhi Rong; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Inamura, Kentaro; Nishihara, Reiko; Yamauchi, Mai; Lochhead, Paul; Qian, Zhi Rong; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Inamura, Kentaro; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Inamura, Kentaro] Japanese Fdn Canc Res, Inst Canc, Div Pathol, Tokyo 170, Japan.
[Song, Mingyang; Nishihara, Reiko; Giovannucci, Edward; Wu, Kana] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA.
[Song, Mingyang; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Nishihara, Reiko] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Jung, Seungyoun; Zhang, Xuehong; Giovannucci, Edward; Fuchs, Charles S.; Cho, Eunyoung; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Lochhead, Paul; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA.
[Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI USA.
RP Wu, KN (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA.; Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA.
EM kana.wu@channing.harvard.edu; shuji_ogino@dfci.harvard.edu
FU National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, UM1
CA167552, UM1 CA186107, P50 CA127003, R01 CA136950, R01 CA137178, K24
DK098311, R01 CA151993, R35 CA197735, K07 CA190673]; Paula and Russell
Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber
Cancer Institute; Entertainment Industry Foundation through National
Colorectal Cancer Research Alliance; Japan Society for the Promotion of
Science; Takashi Tsuruo Memorial Fund; Harvard University Frank Knox
Memorial Fellowship; Asan Medical Center; Uehara Memorial Foundation
FX This work was supported by National Institutes of Health (NIH) grants
(P01 CA87969 to SEH; P01 CA55075 to WCW; UM1 CA167552 to WCW; UM1
CA186107 to MJS; P50 CA127003 to CSF; R01 CA136950 to EC; R01 CA137178
and K24 DK098311 to ATC; R01 CA151993 and R35 CA197735 to SO; and K07
CA190673 to RN) and by grants from the Paula and Russell Agrusa Fund for
Colorectal Cancer Research (to CSF), the Friends of the Dana-Farber
Cancer Institute (to SO), and the Entertainment Industry Foundation
through National Colorectal Cancer Research Alliance. KI was supported
by a Japan Society for the Promotion of Science Postdoctoral Fellowship
for Research Abroad and by Takashi Tsuruo Memorial Fund. MS is a trainee
of the Harvard Transdisciplinary Research Center on Energetics and
Cancer (TREC). PL is a Scottish Government Clinical Academic Fellow and
was supported by a Harvard University Frank Knox Memorial Fellowship.
SAK was supported by an early exchange postdoctoral fellowship grant
from Asan Medical Center. KM is supported by a fellowship grant from the
Uehara Memorial Foundation. ATC is a Damon Runyon Clinical Investigator.
NR 63
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U1 2
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD APR
PY 2016
VL 108
IS 4
AR djv363
DI 10.1093/jnci/djv363
PG 10
WC Oncology
SC Oncology
GA DK6RR
UT WOS:000375053400025
ER
PT J
AU Land, SR
Walcott, FL
Liu, Q
Wickerham, DL
Costantino, JP
Ganz, PA
AF Land, Stephanie R.
Walcott, Farzana L.
Liu, Qing
Wickerham, D. Lawrence
Costantino, Joseph P.
Ganz, Patricia A.
TI Symptoms and QOL as Predictors of Chemoprevention Adherence in NRG
Oncology/NSABP Trial P-1
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; CANCER PREVENTION TRIAL; BOWEL PROJECT P-1;
QUALITY-OF-LIFE; CIGARETTE-SMOKING; ENDOCRINE THERAPY;
PHYSICAL-ACTIVITY; TAMOXIFEN USE; US WOMEN; RISK
AB Background: Tamoxifen provides a 50% reduction in the incidence of breast cancer (BC) among high-risk women, yet many do not adhere to the five-year course of therapy. Using the prospective double-blind National Surgical Adjuvant Breast and Bowel Project P-1 study, we evaluated whether participant-reported outcomes were associated with drug adherence and whether baseline behavioral risk factors modified those associations.
Methods: P-1 participants were randomly assigned to placebo vs tamoxifen (20 mg/day). Mixed effects logistic regression was used to evaluate whether baseline or three-month SF-36 quality of life (QOL) mental and physical component summaries (MCS, PCS), and participant-reported symptoms (gynecologic, vasomotor, sexual, and other) predicted 12-month drug adherence (76-100% of assigned medication). The evaluation accounted for age, treatment, estimated breast cancer risk, education, baseline smoking, alcohol consumption, and obesity. All statistical tests were two-sided.
Results: Participants enrolled at least three years before trial unblinding and without medically indicated discontinuation before 12 months were eligible for the present analyses (n = 10 576). At 12 months, 84.3% were adherent. Statistically significant predictors of adherence were: three-month MCS (odds ratio [OR] = 1.15 per 10 points, 95% confidence interval [CI] = 1.06 to 1.25); three-month gynecologic symptoms among moderate alcohol drinkers (OR = .79, 95% CI = 0.72 to 0.88); baseline vasomotor symptoms among participants assigned tamoxifen (OR = .88, 95% CI = 0.80 to 0.97); and three-month sexual symptoms among younger participants (OR = .89 at age 41 years, 95% CI = 0.80 to 0.99). The strongest association was with three-month other symptoms (OR = .77, 95% CI = 0.63 to 0.93). PCS was not associated with adherence. Symptom and QOL associations were not modified by smoking or obesity.
Conclusions: Promoting QOL and managing symptoms early in therapy may be important strategies to improve adherence.
C1 [Land, Stephanie R.; Wickerham, D. Lawrence; Ganz, Patricia A.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
[Land, Stephanie R.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Walcott, Farzana L.] NCI, Canc Prevent Div, Rockville, MD USA.
[Liu, Qing; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Wickerham, D. Lawrence] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Dept Hlth Serv, Los Angeles, CA 90024 USA.
RP Land, SR (reprint author), 9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM stephanie.land@nih.gov
FU Public Health Service from the National Cancer Institute, Department of
Health and Human Services [U10-CA-37377, U10-CA-69974, U10-CA-180868,
U10-CA-180822, UG1-CA-189867, R03CA134199-02]
FX This work was supported by: Public Health Service Grants U10-CA-37377
(SRL, DLW, JPC, PAG) and U10-CA-69974 (SRL, DLW, JPC, PAG);
U10-CA-180868 and U10-CA-180822 (NRG Oncology); UG1-CA-189867 (NCORP);
R03CA134199-02 (SRL, PAG) from the National Cancer Institute, Department
of Health and Human Services, and Zeneca Pharmaceuticals (which supplied
tamoxifen/placebo).
NR 33
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Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD APR
PY 2016
VL 108
IS 4
AR djv365
DI 10.1093/jnci/djv365
PG 6
WC Oncology
SC Oncology
GA DK6RR
UT WOS:000375053400027
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI Scientific Realism and the Patent System
SO JOURNAL FOR GENERAL PHILOSOPHY OF SCIENCE
LA English
DT Article
DE Patents; Inventions; Realism; Anti-realism; Nature; Causation
ID ANTICOMMONS
AB The patent system appears to make three ontological assumptions often associated with scientific realism: there is a natural world that is independent of human knowledge and technology; invented products can be unobservable things; and invented products have causal powers. Although a straightforward reading of patent laws implies these ontological commitments, it is not at all clear that what the patent system has to say about the world has any bearing on issues of scientific realism. While realists might embrace the patent system's apparent ontology as providing additional support for their view, anti-realists could propose an alternative interpretation of patent law that does not involve realist ontological commitments. Thus, questions about the patent system's ontology depend on whether one takes patent laws at face value or defends an interpretation of patent law motivated by philosophical theory. Philosophers of science should pay attention to the practice of patenting, even if they ultimately reject the patent system's apparent ontology and offer an alternative interpretation.
C1 [Resnik, David B.] NIEHS, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
NR 31
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Z9 0
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-4560
EI 1572-8587
J9 J GEN PHILOS SCI
JI J. Gen. Philos. Sci.
PD APR
PY 2016
VL 47
IS 1
BP 69
EP 77
DI 10.1007/s10838-016-9326-z
PG 9
WC History & Philosophy Of Science
SC History & Philosophy of Science
GA DK3TA
UT WOS:000374839100005
ER
PT J
AU Takeda, T
Wang, YL
Bryant, SH
AF Takeda, Takako
Wang, Yanli
Bryant, Stephen H.
TI Structural insights of a PI3K/mTOR dual inhibitor with the
morpholino-triazine scaffold
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE PI3K; mTOR; Pharmacophore; 3D-QSAR; Docking; PKI-587
ID HUMAN HEAD; IN-VIVO; PKI-587; PI3K; IDENTIFICATION; LESSONS; MODELS;
TARGET
AB Stimulation of the PI3K/Akt/mTOR pathway, which controls cell proliferation and growth, is often observed in cancer cell. Inhibiting both PI3K and mTOR in this pathway can switch off Akt activation and hence, plays a powerful role for modulating this pathway. PKI-587, a drug containing the structure of morpholino-triazines, shows a dual and nano-molar inhibition activity and is currently in clinical trial. To provide an insight into the mechanism of this dual inhibition, pharmacophore and QSAR models were developed in this work using compounds based on the morpholino-triazines scaffold, followed by a docking study. Pharmacophore model suggested the mechanism of the inhibition of PI3K alpha and mTOR by the compounds were mostly the same, which was supported by the docking study showing similar docking modes. The analysis also suggested the importance of the flat plane shape of the ligands, the space surrounding the ligands in the binding pocket, and the slight difference in the shape of the binding sites between PI3K alpha and mTOR.
C1 [Takeda, Takako; Wang, Yanli; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH)
National Library of Medicine (NLM); NIGMS [P41-GM103311]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH) National Library of Medicine (NLM).
This study utilized the high-performance computational capabilities of
the Biowulf Linux cluster at the National Institutes of Health,
Bethesda, MD. (http://biowulf.nih.gov). The authors acknowledge Dr. Ming
Hao for useful comments on the manuscript. We thank Douglas Joubert, NIH
Library Writing Center, for manuscript editing assistance. Figures 2 and
3 were drawn with the UCSF Chimera package. Chimera is developed by the
Resource for Biocomputing, Visualization, and Informatics at the
University of California, San Francisco (supported by NIGMS
P41-GM103311) [26].
NR 22
TC 0
Z9 0
U1 4
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
EI 1573-4951
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD APR
PY 2016
VL 30
IS 4
BP 323
EP 330
DI 10.1007/s10822-016-9905-4
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA DJ7SY
UT WOS:000374413900005
PM 26956874
ER
PT J
AU Yuan, WP
Cheng, SM
Fu, WT
Zhao, M
Li, XB
Cai, YP
Dong, JY
Huang, KX
Gustafson, KR
Yan, PC
AF Yuan, Weiping
Cheng, Shimiao
Fu, Weitao
Zhao, Min
Li, Xiubao
Cai, Yuepiao
Dong, Jianyong
Huang, Kexin
Gustafson, Kirk R.
Yan, Pengcheng
TI Structurally Diverse Metabolites from the Soft Coral Sinularia verruca
Collected in the South China Sea
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID NATURAL-PRODUCTS; LOBOPHYTUM SP; CEMBRANOIDS; CAPILLOSA; CYCLOPENTENONE;
DERIVATIVES; FLEXIBILIS; HIV-1
AB Nineteen metabolites with diverse structures, including the rare pyrroloindoline alkaloid verrupyrroloindoline (1), the unprecedented highly fused benzosesquiterpenoid verrubenzospirolactone (2), the new asteriscane-type sesquiterpenoid 10-deoxocapillosanane D (3), and the two new cyclopentenone derivatives (4S*,5S*)-4-hydroxy-5-(hydroxymethyl)-2,3-dimethyl-4-pentylcydopent-2-en-1-one (4) and (S)-4-hydroxy-5-methylene-2,3dimethyl-4-pentylcydopent-2-en-1-one (5), were isolated from a South China Sea collection of the soft coral Sinularia verruca. Eleven previously described marine metabolites (7-15, 18, and 19) were also obtained as well as three new EtOH-adduct artifacts (6, 16, and 17). The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 4, 5, and 16 showed protection against the cytopathic effects of HIV-1 infection with EC50 values of 5.8-34 mu M, and 4, 6, and 16 exhibited inhibition against LPS-induced NO production with IC50 values of 24-28 mu M.
C1 [Yuan, Weiping; Fu, Weitao; Zhao, Min; Cai, Yuepiao; Dong, Jianyong; Huang, Kexin; Yan, Pengcheng] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China.
[Cheng, Shimiao] Wenzhou Med Univ, Affiliated Hosp 5, Lishui 323000, Zhejiang, Peoples R China.
[Li, Xiubao] Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Marine Bioresources Sustainable Utilizat, Guangzhou 510301, Guangdong, Peoples R China.
[Gustafson, Kirk R.; Yan, Pengcheng] NCI, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
RP Yan, PC (reprint author), Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China.; Gustafson, KR; Yan, PC (reprint author), NCI, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
EM gustafki@mail.nih.gov; yanpc@wzmc.edu.cn
FU NSFC [21202123]; ZJNSF [LQ12B02002]; CSC [201408330121]; Wenzhou Medical
University [QTJ10018]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This work was supported by grants from NSFC (No. 21202123), ZJNSF (No.
LQ12B02002), CSC (No. 201408330121), and Start-Up Funding from Wenzhou
Medical University (No. QTJ10018). This research was also supported in
part by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 24
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Z9 0
U1 2
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD APR
PY 2016
VL 79
IS 4
BP 1124
EP 1131
DI 10.1021/acs.jnatprod.6b00031
PG 8
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA DK4UM
UT WOS:000374915800056
PM 27010413
ER
PT J
AU Choi, Y
Abdelmegeed, MA
Akbar, M
Song, BJ
AF Choi, Youngshim
Abdelmegeed, Mohamed A.
Akbar, Mohammed
Song, Byoung-Joon
TI Dietary walnut reduces hepatic triglyceride content in high-fat-fed mice
via modulation of hepatic fatty acid metabolism and adipose tissue
inflammation
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Walnut; High-fat diet; Liver; Steatosis; Triglyceride; Adipose tissue;
Inflammation
ID NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; LIVER-DISEASE; NONALCOHOLIC
STEATOHEPATITIS; MACROPHAGE INFILTRATION; ADIPOCYTE DEATH;
GENE-EXPRESSION; INDUCED OBESITY; DEFICIENT MICE; STEATOSIS
AB In this study, we evaluated the protective effects of dietary walnuts on high-fat diet (HFD)-induced fatty liver and studied the underlying mechanisms. Male C57BL/6J mice were fed either a regular rodent chow or HFD (45% energy-derived) with or without walnuts (21.5% energy-derived) for 20 weeks. Walnut supplementation did not change HFD-induced increase in body weight or visceral fat mass. However, dietary walnuts significantly decreased the amounts of hepatic triglyceride (TG) observed in HFD-fed mice. The addition of walnuts significantly altered the levels of proteins, involved in the hepatic lipid homeostasis, including AMP-activated protein kinase, fatty acid synthase and peroxisome proliferator-activated receptor-a. Since adipocyte inflammation and apoptosis are reportedly important in regulating hepatic fat accumulation, we also evaluated the protective effects of walnuts on adipose tissue injury. Real-time polymerase chain reaction results revealed that adipose tissues isolated from mice fed the HFD + walnut diets showed significantly decreased levels of macrophage infiltration with suppressed expression of proinflammatory genes compared to those significantly elevated in mice fed HFD alone. These improvements also coincided with reduction of HFD-induced apoptosis of adipocytes by dietary walnuts. However, the supplemented walnuts did not significantly alter HFD-induced peripheral glucose intolerance or insulin resistance despite a trend of improvement. Collectively, these results demonstrate that the protective effects of walnuts against HFD-induced hepatic TG accumulation in mice are mediated, at least partially, by modulating the key proteins in hepatic lipid homeostasis and suppression of the genes related to adipose tissue inflammation and macrophage infiltration as well as prevention of adipocyte apoptosis. Published by Elsevier Inc.
C1 [Choi, Youngshim; Abdelmegeed, Mohamed A.; Akbar, Mohammed; Song, Byoung-Joon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bj.song@nih.gov
FU National Institute on Alcohol Abuse and Alcoholism; KRIBB Research
Initiative Program (Korean Biomedical Scientist Fellowship Program),
Korea Research Institute of Bioscience and Biotechnology, Republic of
Korea
FX This research was supported by the Intramural Program of National
Institute on Alcohol Abuse and Alcoholism. This work was also supported
by a grant to Youngshim Choi from the KRIBB Research Initiative Program
(Korean Biomedical Scientist Fellowship Program), Korea Research
Institute of Bioscience and Biotechnology, Republic of Korea. The
authors are thankful to Dr. Klaus Gawrisch for supporting this study.
NR 64
TC 2
Z9 2
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD APR
PY 2016
VL 30
BP 116
EP 125
DI 10.1016/j.jnutbio.2015.12.005
PG 10
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA DJ6TY
UT WOS:000374347300013
PM 27012628
ER
PT J
AU Ortiz, MV
Meier, ER
Hsieh, MM
AF Ortiz, Michael V.
Meier, Emily R.
Hsieh, Matthew M.
TI Identification and Clinical Characterization of Children With Benign
Ethnic Neutropenia
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE neutropenia; benign ethnic neutropenia; pediatric hematology; oncology
ID YEMENITE-JEWS; BONE-MARROW
AB Benign ethnic neutropenia (BEN) is an asymptomatic condition reported in adults of African and Middle Eastern descent. The clinical description in children is currently lacking. In our urban outpatient pediatric hematology clinic, the median neutrophil count of children with BEN was lower than previous reports in adults at 893x10(6) cells/L, but increased with older age. There was an equal male to female ratio and 24% of our BEN children reported ethnicities other than African or Middle Eastern. Children with BEN had a clinical course comparable with other healthy children including otherwise normal blood counts, except for mild anemia.
C1 [Ortiz, Michael V.; Meier, Emily R.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Meier, Emily R.] George Washington Sch Med & Hlth Sci, Dept Pediat, Washington, DC USA.
[Ortiz, Michael V.] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave,POB 139, New York, NY 10065 USA.
[Ortiz, Michael V.] Weill Cornell Med Ctr, New York Presbyterian, Div Pediat Hematol & Oncol, New York, NY USA.
[Meier, Emily R.] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA.
[Hsieh, Matthew M.] NIDDK, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA.
[Hsieh, Matthew M.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ortiz, Michael V.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Ortiz, Michael V.] Weill Cornell Med Ctr, New York Presbyterian, New York, NY USA.
[Meier, Emily R.] Indiana Hemophilia & Thrombosis Ctr Inc, 8326 Naab Rd, Indianapolis, IN 46260 USA.
RP Ortiz, MV (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave,POB 139, New York, NY 10065 USA.; Ortiz, MV (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.; Ortiz, MV (reprint author), Weill Cornell Med Ctr, New York Presbyterian, New York, NY USA.
EM ortizm2@mskcc.org
FU Intramural NIH HHS [Z99 HL999999]
NR 14
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1077-4114
EI 1536-3678
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD APR
PY 2016
VL 38
IS 3
BP E140
EP E143
DI 10.1097/MPH.0000000000000528
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DK2XO
UT WOS:000374777900012
PM 26925714
ER
PT J
AU Dhavle, AA
Ward-Charlerie, S
Rupp, MT
Kilbourne, J
Amin, VP
Ruiz, J
AF Dhavle, Ajit A.
Ward-Charlerie, Stacy
Rupp, Michael T.
Kilbourne, John
Amin, Vishal P.
Ruiz, Joshua
TI Evaluating the implementation of RxNorm in ambulatory electronic
prescriptions
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
DE RxNorm; E-Prescribing; electronic prescriptions; NDC; quality
ID CONTROLLED MEDICAL VOCABULARIES; CONSEQUENCES; DESIDERATA; PHARMACIES
AB Methods We analyzed a random sample of 49 997 e-prescriptions that were received by 7391 locations of a national retail pharmacy chain during a single day in April 2014. The e-prescriptions in the sample were generated by 37 801 ambulatory care prescribers using 519 different e-prescribing software applications.
Results We found that 97.9% of e-prescriptions in the study sample could be accurately represented by an RxNorm identifier. However, RxNorm identifiers were actually used as drug identifiers in only 16 433 (33.0%) e-prescriptions. Another 431 (2.5%) e-prescriptions that used RxNorm identifiers had a discrepancy in the corresponding Drug Database Code qualifier field or did not have a qualifier (Term Type) at all. In 10 e-prescriptions (0.06%), the free-text drug description and the RxNorm concept unique identifier pointed to completely different drug concepts, and in 7 e-prescriptions (0.04%), the NDC and RxNorm drug identifiers pointed to completely different drug concepts.
Discussion The National Library of Medicine continues to enhance the RxNorm terminology and expand its scope. This study illustrates the need for technology vendors to improve their implementation of RxNorm; doing so will accelerate the adoption of RxNorm as the preferred alternative to using the NDC terminology in e-prescribing.
C1 [Dhavle, Ajit A.; Ward-Charlerie, Stacy; Ruiz, Joshua] Surescripts LLC, Clin Qual, Arlington, VA 22202 USA.
[Rupp, Michael T.] Midwestern Univ, Pharm Adm, Glendale, AZ USA.
[Kilbourne, John] Natl Lib Med, Med Subject Headings MeSH, Bethesda, MD USA.
[Amin, Vishal P.] CVS Hlth Patient Safety & Qual Assurance, Woonsocket, RI USA.
RP Dhavle, AA (reprint author), Surescripts LLC, 2800 Crystal Dr, Arlington, VA 22202 USA.
EM ajit.dhavle@surescripts.com
NR 26
TC 0
Z9 0
U1 2
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD APR
PY 2016
VL 23
IS E1
BP E99
EP E107
DI 10.1093/jamia/ocv131
PG 9
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA DL0AD
UT WOS:000375292600014
PM 26510879
ER
PT J
AU Laverdure, S
Polakowski, N
Hoang, K
Lemasson, I
AF Laverdure, Sylvain
Polakowski, Nicholas
Hoang, Kimson
Lemasson, Isabelle
TI Permissive Sense and Antisense Transcription from the 5 ' and 3 ' Long
Terminal Repeats of Human T-Cell Leukemia Virus Type 1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIPPER FACTOR HBZ; NF-KAPPA-B; BZIP
FACTOR; VIRAL TRANSCRIPTION; CPG METHYLATION; TAX PROTEIN; IN-VITRO;
HTLV-1; GENE
AB Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus, and, as such, its genome becomes chromosomally integrated following infection. The resulting provirus contains identical 5' and 3' peripheral long terminal repeats (LTRs) containing bidirectional promoters. Antisense transcription from the 3' LTR regulates expression of a single gene, hbz, while sense transcription from the 5' LTR controls expression of all other viral genes, including tax. Both the HBZ and Tax proteins are implicated in the development of adult T-cell leukemia (ATL), a T-cell malignancy caused by HTLV-1 infection. However, these proteins appear to harbor opposing molecular functions, indicating that they may act independently and at different time points prior to leukemogenesis. Here, we used bidirectional reporter constructs to test whether transcriptional interference serves as a mechanism that inhibits simultaneous expression of Tax and HBZ. We found that sense transcription did not interfere with antisense transcription from the 3' LTR and vice versa, even with strong transcription emanating from the opposing direction. Therefore, bidirectional transcription across the provirus might not restrict hbz or tax expression. Single-cell analyses revealed that antisense transcription predominates in the absence of Tax, which transactivates viral sense transcription. Interestingly, a population of Tax-expressing cells exhibited antisense but not activated sense transcription. Consistent with the ability of Tax to induce cell cycle arrest, this population was arrested in G(0)/G(1) phase. These results imply that cell cycle arrest inhibits Tax-mediated activation of sense transcription without affecting antisense transcription, which may be important for long-term viral latency.
C1 [Laverdure, Sylvain; Polakowski, Nicholas; Hoang, Kimson; Lemasson, Isabelle] E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC USA.
[Laverdure, Sylvain] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Laverdure, S; Lemasson, I (reprint author), E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC USA.
EM sylvain.laverdure@nih.gov; lemassoni@ecu.edu
FU HHS \ NIH \ National Cancer Institute (NCI) [CA128800]
FX HHS vertical bar NIH vertical bar National Cancer Institute (NCI)
provided funding to Isabelle Lemasson under grant number CA128800.
NR 50
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2016
VL 90
IS 7
BP 3600
EP 3610
DI 10.1128/JVI.02634-15
PG 11
WC Virology
SC Virology
GA DK7QQ
UT WOS:000375121200027
PM 26792732
ER
PT J
AU Eller, MA
Goonetilleke, N
Tassaneetrithep, B
Eller, LA
Costanzo, MC
Johnson, S
Betts, MR
Krebs, SJ
Slike, BM
Nitayaphan, S
Rono, K
Tovanabutra, S
Maganga, L
Kibuuka, H
Jagodzinski, L
Peel, S
Rolland, M
Marovich, MA
Kim, JH
Michael, NL
Robb, ML
Streeck, H
AF Eller, Michael A.
Goonetilleke, Nilu
Tassaneetrithep, Boonrat
Eller, Leigh Anne
Costanzo, Margaret C.
Johnson, Susan
Betts, Michael R.
Krebs, Shelly J.
Slike, Bonnie M.
Nitayaphan, Sorachai
Rono, Kathleen
Tovanabutra, Sodsai
Maganga, Lucas
Kibuuka, Hannah
Jagodzinski, Linda
Peel, Sheila
Rolland, Morgane
Marovich, Mary A.
Kim, Jerome H.
Michael, Nelson L.
Robb, Merlin L.
Streeck, Hendrik
TI Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC VIRAL-INFECTION; ANTIRETROVIRAL
THERAPY; TYPE-1 INFECTION; DISEASE PROGRESSION; CD27 EXPRESSION; SIV
INFECTION; HEPATITIS-B; RESPONSES; VIREMIA
AB Attrition within the CD4(+) T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8(+) T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8(+) T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38(+) CD27- CD8(+) T cells characterized by the low expression of the CD8 receptor (CD8(dim)). Interestingly, while high frequencies of HIV-specific CD8(+) T cell responses occur within the CD38(+) CD27(-) CD8(dim) T cell population, the minority populations of CD8(bright) T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8(dim) T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8(dim) T cells, and the size of this population inversely correlates with the acute loss of CD4(+) T cells. These data indicate, for the first time, that early CD4(+) T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8(dim) T cell population less efficient in controlling HIV viremia.
IMPORTANCE
A distinct population of activated CD8(+) T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8(+) T cell dysfunction during acute infection.
C1 [Eller, Michael A.; Eller, Leigh Anne; Costanzo, Margaret C.; Johnson, Susan; Krebs, Shelly J.; Slike, Bonnie M.; Tovanabutra, Sodsai; Jagodzinski, Linda; Peel, Sheila; Rolland, Morgane; Marovich, Mary A.; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin L.; Streeck, Hendrik] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Eller, Michael A.; Eller, Leigh Anne; Costanzo, Margaret C.; Johnson, Susan; Krebs, Shelly J.; Slike, Bonnie M.; Tovanabutra, Sodsai; Rolland, Morgane; Robb, Merlin L.; Streeck, Hendrik] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Goonetilleke, Nilu] Univ N Carolina, Dept Immunol & Microbiol, Chapel Hill, NC USA.
[Tassaneetrithep, Boonrat] Mahidol Univ, Siriraj Hosp, Fac Med, Off Res & Dev, Bangkok 10700, Thailand.
[Betts, Michael R.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Nitayaphan, Sorachai] USAMC AFRIMS, Dept Retrovirol, Bangkok, Thailand.
[Rono, Kathleen] Walter Reed Project Kenya, Kericho, Kenya.
[Maganga, Lucas] Walter Reed Program Tanzania, Mbeya, Tanzania.
[Kibuuka, Hannah] Makerere Univ, Walter Reed Project, Kampala, Uganda.
[Streeck, Hendrik] Univ Duisburg Essen, Univ Hosp Essen, Inst HIV Res, Essen, Germany.
[Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea.
[Marovich, Mary A.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Streeck, H (reprint author), Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.; Streeck, H (reprint author), Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.; Streeck, H (reprint author), Univ Duisburg Essen, Univ Hosp Essen, Inst HIV Res, Essen, Germany.
EM Hendrik.streeck@uk-essen.de
FU Henry M. Jackson Foundation for the Advancement of Military Medicine,
Inc. [W81XWH-11-2-0174]; U.S. Department of Defense (DoD)
[W81XWH-11-2-0174]
FX This work was supported by a cooperative agreement (W81XWH-11-2-0174)
between the Henry M. Jackson Foundation for the Advancement of Military
Medicine, Inc., and the U.S. Department of Defense (DoD).
NR 38
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U1 1
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PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2016
VL 90
IS 8
BP 4005
EP 4016
DI 10.1128/JVI.02785-15
PG 12
WC Virology
SC Virology
GA DK7RQ
UT WOS:000375123800019
PM 26842474
ER
PT J
AU Asbach, B
Kliche, A
Kostler, J
Perdiguero, B
Esteban, M
Jacobs, BL
Montefiori, DC
LaBranche, CC
Yates, NL
Tomaras, GD
Ferrari, G
Foulds, KE
Roederer, M
Landucci, G
Forthal, DN
Seaman, MS
Hawkins, N
Self, SG
Sato, A
Gottardo, R
Phogat, S
Tartaglia, J
Barnett, SW
Burke, B
Cristillo, AD
Weiss, DE
Francis, J
Galmin, L
Ding, S
Heeney, JL
Pantaleo, G
Wagner, R
AF Asbach, Benedikt
Kliche, Alexander
Koestler, Josef
Perdiguero, Beatriz
Esteban, Mariano
Jacobs, Bertram L.
Montefiori, David C.
LaBranche, Celia C.
Yates, Nicole L.
Tomaras, Georgia D.
Ferrari, Guido
Foulds, Kathryn E.
Roederer, Mario
Landucci, Gary
Forthal, Donald N.
Seaman, Michael S.
Hawkins, Natalie
Self, Steven G.
Sato, Alicia
Gottardo, Raphael
Phogat, Sanjay
Tartaglia, James
Barnett, Susan W.
Burke, Brian
Cristillo, Anthony D.
Weiss, Deborah E.
Francis, Jesse
Galmin, Lindsey
Ding, Song
Heeney, Jonathan L.
Pantaleo, Giuseppe
Wagner, Ralf
TI Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost
HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; RECOMBINANT ADENOVIRAL VECTORS; PHASE-I TRIAL;
CLADE-C; NEUTRALIZING ANTIBODIES; EFFICACY TRIAL; NYVAC-C; PROTECTIVE
EFFICACY; NONHUMAN-PRIMATES; IMMUNE-RESPONSES
AB In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the pox-viral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8(+) and CD4(+) T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings.
IMPORTANCE
Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols.
C1 [Asbach, Benedikt; Kliche, Alexander; Wagner, Ralf] Univ Regensburg, Inst Med Microbiol & Hyg, D-93053 Regensburg, Germany.
[Koestler, Josef] Univ Regensburg, Inst Clin Microbiol & Hyg, D-93053 Regensburg, Germany.
[Perdiguero, Beatriz; Esteban, Mariano] CSIC, Dept Mol & Cellular Biol, Ctr Nacl Biotecnol, Madrid, Spain.
[Jacobs, Bertram L.] Arizona State Univ, Biodesign Inst, Tempe, AZ USA.
[Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido] Duke Univ, Med Ctr, Durham, NC USA.
[Foulds, Kathryn E.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.
[Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Hawkins, Natalie; Self, Steven G.; Sato, Alicia; Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, 1124 Columbia St, Seattle, WA 98104 USA.
[Phogat, Sanjay; Tartaglia, James] Sanofi Pasteur, Swiftwater, PA USA.
[Barnett, Susan W.; Burke, Brian] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Cristillo, Anthony D.; Weiss, Deborah E.; Francis, Jesse; Galmin, Lindsey] Adv BioSci Labs Inc, Rockville, MD USA.
[Ding, Song] EuroVacc Fdn, Lausanne, Switzerland.
[Heeney, Jonathan L.] Univ Cambridge, Dept Vet Med, Lab Viral Zoonot, Cambridge, England.
[Pantaleo, Giuseppe] Univ Lausanne, CHU Vaudois, Dept Med, Div Immunol & Allergy, Lausanne, Switzerland.
[Weiss, Deborah E.] Bioqual Inc, Rockville, MD USA.
RP Wagner, R (reprint author), Univ Regensburg, Inst Med Microbiol & Hyg, D-93053 Regensburg, Germany.
EM ralf.wagner@klinik.uni-regensburg.de
RI Tomaras, Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016
FU Bill & Melinda Gates Foundation Poxvirus T-Cell Vaccine Discovery
Consortium (PTVDC) [38599]; Vaccine Immune Monitoring Centers
[OPP1032144, OPP1032325]; Vaccine Immunology Statistical Center as part
of the Collaboration for AIDS Vaccine Discovery (CAVD) [OPP1032317];
Bill & Melinda Gates Foundation; DAIDS [HHSN266200500007C]; NIAID; NIH
FX This investigation was funded by the Bill & Melinda Gates Foundation
Poxvirus T-Cell Vaccine Discovery Consortium (PTVDC) (grant 38599). The
Vaccine Immune Monitoring Centers (grants OPP1032144 and OPP1032325) and
the Vaccine Immunology Statistical Center (grant OPP1032317), as part of
the Collaboration for AIDS Vaccine Discovery (CAVD), were funded by the
Bill & Melinda Gates Foundation. Novartis Vaccines received support for
this work under contract number HHSN266200500007C from DAIDS, NIAID,
NIH.
NR 70
TC 1
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U1 3
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2016
VL 90
IS 8
BP 4133
EP 4149
DI 10.1128/JVI.03135-15
PG 17
WC Virology
SC Virology
GA DK7RQ
UT WOS:000375123800030
PM 26865719
ER
PT J
AU Bamunusinghe, D
Naghashfar, Z
Buckler-White, A
Plishka, R
Baliji, S
Liu, QP
Kassner, J
Oler, AJ
Hartley, J
Kozak, CA
AF Bamunusinghe, Devinka
Naghashfar, Zohreh
Buckler-White, Alicia
Plishka, Ronald
Baliji, Surendranath
Liu, Qingping
Kassner, Joshua
Oler, Andrew J.
Hartley, Janet
Kozak, Christine A.
TI Sequence Diversity, Intersubgroup Relationships, and Origins of the
Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FOCUS-FORMING VIRUSES; MUS MUSCULUS CASTANEUS; CELL-SURFACE RECEPTOR;
PROLINE-RICH REGION; HOST-RANGE; XENOTROPIC GAMMARETROVIRUSES;
NUCLEOTIDE-SEQUENCE; RETROVIRUS XMRV; ECOTROPIC VIRUS; MURINE
RETROVIRUSES
AB Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies of Mus musculus. Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions of env produced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome. env variations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region of env. Outside the env region, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributed Mus subspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents.
IMPORTANCE
Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter-and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution.
C1 [Bamunusinghe, Devinka; Buckler-White, Alicia; Plishka, Ronald; Baliji, Surendranath; Liu, Qingping; Kassner, Joshua; Kozak, Christine A.] NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Naghashfar, Zohreh; Hartley, Janet] NIAID, Immunogenet Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Oler, Andrew J.] NIAID, Bioinformat & Computat Biosci Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Baliji, Surendranath] Bayer CropSci, Nunhems USA, Acampo, CA USA.
RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
FU HHS\ NIH \ National Institute of Allergy and Infectious Diseases (NIAID)
[AI000300-34]
FX HHS vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Devinka Bamunusinghe,
Alicia Buckler-White, Ronald Plishka, Surendranath Baliji, Qingping Liu,
Joshua Kassner, and Christine Kozak under grant number AI000300-34.
NR 83
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PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2016
VL 90
IS 8
BP 4186
EP 4198
DI 10.1128/JVI.03186-15
PG 13
WC Virology
SC Virology
GA DK7RQ
UT WOS:000375123800034
PM 26865715
ER
PT J
AU Alfano, N
Kolokotronis, SO
Tsangaras, K
Roca, AL
Xu, WQ
Eiden, MV
Greenwood, AD
AF Alfano, Niccolo
Kolokotronis, Sergios-Orestis
Tsangaras, Kyriakos
Roca, Alfred L.
Xu, Wenqin
Eiden, Maribeth V.
Greenwood, Alex D.
TI Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape
Leukemia Virus and Related Gammaretroviruses (vol 90, pg 1757, 2016)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Alfano, Niccolo; Tsangaras, Kyriakos; Greenwood, Alex D.] Leibniz Inst Zoo & Wildlife Res, Berlin, Germany.
[Kolokotronis, Sergios-Orestis] Fordham Univ, Dept Biol Sci, Bronx, NY 10458 USA.
[Kolokotronis, Sergios-Orestis] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
[Kolokotronis, Sergios-Orestis] Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA.
[Roca, Alfred L.] Univ Illinois, Dept Anim Sci, Urbana, IL USA.
[Xu, Wenqin; Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
[Greenwood, Alex D.] Free Univ Berlin, Dept Vet Med, Berlin, Germany.
RP Alfano, N (reprint author), Leibniz Inst Zoo & Wildlife Res, Berlin, Germany.
NR 1
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U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2016
VL 90
IS 8
BP 4254
EP 4254
DI 10.1128/JVI.00210-16
PG 1
WC Virology
SC Virology
GA DK7RQ
UT WOS:000375123800040
PM 27022099
ER
PT J
AU Ryu, S
Atzmon, G
Barzilai, N
Raghavachari, N
Suh, Y
AF Ryu, Seungjin
Atzmon, Gil
Barzilai, Nir
Raghavachari, Nalini
Suh, Yousin
TI Genetic landscape of APOE in human longevity revealed by high-throughput
sequencing
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE APOE; Centenarian; Genetic variant; Longevity; Pooled target capture
sequencing
ID GENOME-WIDE ASSOCIATION; EXCEPTIONAL LONGEVITY; GENOTYPE; SURVIVAL
AB Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (epsilon 4 allele) or enriched (epsilon 2 allele) in long-lived individuals as compared to controls. We performed high-throughput sequencing analysis of exons and 2 kb proximal promoter of APOE in 450 centenarians and 500 controls of Ashkenazi Jewish decent. We found two common regulatory variants, rs405509 (p = 0.006) and rs769449 (p = 0.036), that were significantly depleted in centenarians. Genotyping analysis of rs7412 and rs429358 showed significant enrichment of epsilon 2 allele (p = 0.003) and epsilon 2/epsilon 3 genotype (p = 0.005), and significant depletion of epsilon 3/epsilon 4 genotype (p = 0.005) in centenarians. Our findings support the hypothesis that variants in both coding and regulatory regions of APOE may contribute to longevity in humans. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Ryu, Seungjin; Atzmon, Gil; Barzilai, Nir; Suh, Yousin] Albert Einstein Coll Med, Dept Genet, 1301 Morris Pk Ave, Bronx, NY 10461 USA.
[Atzmon, Gil; Barzilai, Nir; Suh, Yousin] Albert Einstein Coll Med, Dept Med, 1301 Morris Pk Ave, Bronx, NY 10461 USA.
[Raghavachari, Nalini] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Suh, Yousin] Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10461 USA.
RP Suh, Y (reprint author), Albert Einstein Coll Med, Dept Genet, 1301 Morris Pk Ave, Bronx, NY 10461 USA.; Suh, Y (reprint author), Albert Einstein Coll Med, Dept Med, 1301 Morris Pk Ave, Bronx, NY 10461 USA.
EM yousin.suh@einstein.yu.edu
FU NIH [AG024391, AG027734, AG17242]; Paul F. Glenn Center for the Biology
of Human Aging; Glenn/AFAR Scholarships
FX We would like to thank Archana Tare for critical reading of the
manuscript. This work was funded by NIH grants AG024391, AG027734, and
AG17242 (Y. S.) and a grant from The Paul F. Glenn Center for the
Biology of Human Aging (Y. S.). S. R. is the recipient of a Glenn/AFAR
Scholarships for Research in the Biology of Aging.
NR 15
TC 3
Z9 3
U1 2
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD APR
PY 2016
VL 155
BP 7
EP 9
DI 10.1016/j.mad.2016.02.010
PG 3
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DJ7WE
UT WOS:000374423100002
PM 26930295
ER
PT J
AU Koch, IJ
Clark, MM
Thompson, MJ
Deere-Machemer, KA
Wang, J
Duarte, L
Gnanadesikan, GE
McCoy, EL
Rubbi, L
Stahler, DR
Pellegrini, M
Ostrander, EA
Wayne, RK
Sinsheimer, JS
Vonholdt, BM
AF Koch, Ilana Janowitz
Clark, Michelle M.
Thompson, Michael J.
Deere-Machemer, Kerry A.
Wang, Jun
Duarte, Lionel
Gnanadesikan, Gitanjali E.
McCoy, Eskender L.
Rubbi, Liudmilla
Stahler, Daniel R.
Pellegrini, Matteo
Ostrander, Elaine A.
Wayne, Robert K.
Sinsheimer, Janet S.
Vonholdt, Bridgett M.
TI The concerted impact of domestication and transposon insertions on
methylation patterns between dogs and grey wolves
SO MOLECULAR ECOLOGY
LA English
DT Article
DE canid; domestication; genome regulation; methylation
ID EPIGENOME-WIDE ASSOCIATION; DNA METHYLATION; GENE-EXPRESSION; ANIMAL
DOMESTICATION; EPIGENETIC VARIATION; PERIPHERAL-BLOOD; TRANSGENERATIONAL
INHERITANCE; ARABIDOPSIS-THALIANA; PHENOTYPIC VARIATION; LIFE-HISTORY
AB The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24 000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the grey wolf (Canis lupus). PCA and model-based cluster analyses identified two primary groups, domestic vs. wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hypermethylation typical of purebred dogs when compared to wolves (59% and 58%, P < 0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hypermethylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H-2 and h(2) > 0.99). These analyses provide a unique epigenetic insight into the molecular consequences of recent selection and radiation of our most ancient domesticated companion, the dog. These findings suggest selection has acted on methylation patterns, providing a new genomic perspective on phenotypic diversification in domesticated species.
C1 [Koch, Ilana Janowitz; Deere-Machemer, Kerry A.; Gnanadesikan, Gitanjali E.; Vonholdt, Bridgett M.] Princeton Univ, Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Clark, Michelle M.; Duarte, Lionel; Sinsheimer, Janet S.] Univ Calif Los Angeles, Dept Biostat, UCLA Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA.
[Thompson, Michael J.; Rubbi, Liudmilla; Pellegrini, Matteo] Univ Calif Los Angeles, Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
[Wang, Jun] Wayne State Univ, Dept Biol Sci, Detroit, MI 48085 USA.
[McCoy, Eskender L.] Yale Univ, Sch Management, New Haven, CT 06511 USA.
[Stahler, Daniel R.] Natl Pk Serv, Yellowstone Ctr Resources, Yellowstone Natl Pk, WY 82190 USA.
[Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Wayne, Robert K.] Univ Calif Los Angeles, Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Sinsheimer, Janet S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Biomath, Los Angeles, CA 90095 USA.
RP Vonholdt, BM (reprint author), Princeton Univ, Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM vonHoldt@princeton.edu
RI Gnanadesikan, Gitanjali/I-3571-2016;
OI Gnanadesikan, Gitanjali/0000-0002-1485-5574; Ostrander,
Elaine/0000-0001-6075-9738
FU National Science Foundation [DEB-0613730, DEB-1245373, DMS-1264153];
Yellowstone National Park; Intramural Program of the National Human
Genome Research Institute; AKC OAK (CHF) [1822]; NIH [T32 HG002536,
GM053275]
FX The authors would like to thank the purebred dog owners for providing
blood samples, and Brian Peckinpaugh for providing Boz samples. In
addition, we would like to thank Jennifer Listgarten for providing
support for the program FaST-LMM-EWASher. We would also like to thank
the Princeton University Computational Science & Engineering Support
(CSES) group for providing computational assistance for multiple
components of our work. This study was supported in part by the National
Science Foundation grants DEB-0613730 and DEB-1245373, Yellowstone
National Park, and many donors through the Yellowstone Park Foundation.
This work was also partially funded through the Intramural Program of
the National Human Genome Research Institute and the following
additional grants: AKC OAK (CHF #1822), NIH T32 HG002536, National
Science Foundation DMS-1264153, and NIH GM053275.
NR 148
TC 2
Z9 2
U1 22
U2 52
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1083
EI 1365-294X
J9 MOL ECOL
JI Mol. Ecol.
PD APR
PY 2016
VL 25
IS 8
BP 1838
EP 1855
DI 10.1111/mec.13480
PG 18
WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology;
Evolutionary Biology
GA DK2WY
UT WOS:000374776300016
ER
PT J
AU Day, T
AF Day, Troy
TI Interpreting phenotypic antibiotic tolerance and persister cells as
evolution via epigenetic inheritance
SO MOLECULAR ECOLOGY
LA English
DT Article
DE antibiotic resistance; dormancy; drug resistance; infectious disease;
nongenetic; transgenerational inheritance
ID ESCHERICHIA-COLI; NONGENETIC INHERITANCE; BACTERIAL PERSISTENCE;
DRUG-RESISTANCE; FLUCTUATING ENVIRONMENTS; CHANGING ENVIRONMENTS;
MULTIDRUG TOLERANCE; MECHANISMS; HETEROGENEITY; FREQUENCY
AB Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance.
C1 [Day, Troy] Queens Univ, Dept Math & Stat, Jeffery Hall, Kingston, ON K7L 3N6, Canada.
[Day, Troy] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
[Day, Troy] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Day, T (reprint author), Queens Univ, Dept Math & Stat, Jeffery Hall, Kingston, ON K7L 3N6, Canada.; Day, T (reprint author), Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.; Day, T (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM tday@mast.queensu.ca
FU Research and Policy in Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate; Department of Homeland Security;
Fogarty International Center; National Institutes of Health; Natural
Sciences and Engineering Research Council of Canada
FX I thank the Research and Policy in Infectious Disease Dynamics (RAPIDD)
program of the Science and Technology Directorate, the Department of
Homeland Security, the Fogarty International Center, the National
Institutes of Health, and the Natural Sciences and Engineering Research
Council of Canada for support.
NR 71
TC 2
Z9 2
U1 7
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1083
EI 1365-294X
J9 MOL ECOL
JI Mol. Ecol.
PD APR
PY 2016
VL 25
IS 8
BP 1869
EP 1882
DI 10.1111/mec.13603
PG 14
WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology;
Evolutionary Biology
GA DK2WY
UT WOS:000374776300018
PM 26946044
ER
PT J
AU Cho, N
Moon, EH
Kim, HW
Hong, J
Beutler, JA
Sung, SH
AF Cho, Namki
Moon, Eun Hye
Kim, Hyun Woo
Hong, Jaewoo
Beutler, John A.
Sung, Sang Hyun
TI Inhibition of Nitric Oxide Production in BV2 Microglial Cells by
Triterpenes from Tetrapanax papyriferus
SO MOLECULES
LA English
DT Article
DE Tetrapanax papyriferus; triterpenes; BV2 microglial cells; NO; COX-2
ID LEAVES; FLOWERS; FRUIT
AB It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer's disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-beta-D-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D- and 2D-NMR and MS data. Among these Delta(11,13) oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-alpha and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the Delta(12) oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders.
C1 [Cho, Namki; Moon, Eun Hye; Kim, Hyun Woo; Sung, Sang Hyun] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea.
[Cho, Namki; Moon, Eun Hye; Kim, Hyun Woo; Sung, Sang Hyun] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Cho, Namki; Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Hong, Jaewoo] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Sung, SH (reprint author), Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea.; Sung, SH (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
EM cnamki@naver.com; arsinoe@snu.ac.kr; kimkami2@snu.ac.kr;
jaewoo.hong@nih.gov; beutlerj@mail.nih.gov; shsung@snu.ac.kr
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Science, ICT and Future Planning
[NRF-2013R1A2A2A01016296]; KRIBB Research Initiative Program (Korean
Biomedical Scientist Fellowship Program), Korea Research Institute of
Bioscience and Biotechnology, Republic of Korea; Intramural program of
the NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by the
Ministry of Science, ICT and Future Planning (NRF-2013R1A2A2A01016296).
Additionally, this work was supported by a grant from the KRIBB Research
Initiative Program (Korean Biomedical Scientist Fellowship Program),
Korea Research Institute of Bioscience and Biotechnology, Republic of
Korea and supported in part by the Intramural program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 17
TC 0
Z9 0
U1 3
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD APR
PY 2016
VL 21
IS 4
AR 459
DI 10.3390/molecules21040459
PG 9
WC Chemistry, Organic
SC Chemistry
GA DK8CO
UT WOS:000375155000072
PM 27070561
ER
PT J
AU Couch, FJ
Kuchenbaecker, KB
Michailidou, K
Mendoza-Fandino, GA
Nord, S
Lilyquist, J
Olswold, C
Hallberg, E
Agata, S
Ahsan, H
Aittomaki, K
Ambrosone, C
Andrulis, IL
Anton-Culver, H
Arndt, V
Arun, BK
Arver, B
Barile, M
Barkardottir, RB
Barrowdale, D
Beckmann, L
Beckmann, MW
Benitez, J
Blank, SV
Blomqvist, C
Bogdanova, NV
Bojesen, SE
Bolla, MK
Bonanni, B
Brauch, H
Brenner, H
Burwinkel, B
Buys, SS
Caldes, T
Caligo, MA
Canzian, F
Carpenter, J
Chang-Claude, J
Chanock, SJ
Chung, WK
Claes, KBM
Cox, A
Cross, SS
Cunningham, JM
Czene, K
Daly, MB
Damiola, F
Darabi, H
de la Hoya, M
Devilee, P
Diez, O
Ding, YC
Dolcetti, R
Domchek, SM
Dorfling, CM
dos-Santos-Silva, I
Dumont, M
Dunning, AM
Eccles, DM
Ehrencrona, H
Ekici, AB
Eliassen, H
Ellis, S
Fasching, PA
Figueroa, J
Flesch-Janys, D
Forsti, A
Fostira, F
Foulkes, WD
Friebel, T
Friedman, E
Frost, D
Gabrielson, M
Gammon, MD
Ganz, PA
Gapstur, SM
Garber, J
Gaudet, MM
Gayther, SA
Gerdes, AM
Ghoussaini, M
Giles, GG
Glendon, G
Godwin, AK
Goldberg, MS
Goldgar, DE
Gonzalez-Neira, A
Greene, MH
Gronwald, J
Guenel, P
Gunter, M
Haeberle, L
Haiman, CA
Hamann, U
Hansen, TVO
Hart, S
Healey, S
Heikkinen, T
Henderson, BE
Herzog, J
Hogervorst, FBL
Hollestelle, A
Hooning, MJ
Hoover, RN
Hopper, JL
Humphreys, K
Hunter, DJ
Huzarski, T
Imyanitov, EN
Isaacs, C
Jakubowska, A
James, P
Janavicius, R
Jensen, UB
John, EM
Jones, M
Kabisch, M
Kar, S
Karlan, BY
Khan, S
Khaw, KT
Kibriya, MG
Knight, JA
Ko, YD
Konstantopoulou, I
Kosma, VM
Kristensen, V
Kwong, A
Laitman, Y
Lambrechts, D
Lazaro, C
Lee, E
Le Marchand, L
Lester, J
Lindblom, A
Lindor, N
Lindstrom, S
Liu, J
Long, J
Lubinski, J
Mai, PL
Makalic, E
Malone, KE
Mannermaa, A
Manoukian, S
Margolin, S
Marme, F
Martens, JWM
McGuffog, L
Meindl, A
Miller, A
Milne, RL
Miron, P
Montagna, M
Mazoyer, S
Mulligan, AM
Muranen, TA
Nathanson, KL
Neuhausen, SL
Nevanlinna, H
Nordestgaard, BG
Nussbaum, RL
Offit, K
Olah, E
Olopade, OI
Olson, JE
Osorio, A
Park, SK
Peeters, PH
Peissel, B
Peterlongo, P
Peto, J
Phelan, CM
Pilarski, R
Poppe, B
Pylkas, K
Radice, P
Rahman, N
Rantala, J
Rappaport, C
Rennert, G
Richardson, A
Robson, M
Romieu, I
Rudolph, A
Rutgers, EJ
Sanchez, MJ
Santella, RM
Sawyer, EJ
Schmidt, DF
Schmidt, MK
Schmutzler, RK
Schumacher, F
Scott, R
Senter, L
Sharma, P
Simard, J
Singer, CF
Sinilnikova, OM
Soucy, P
Southey, M
Steinemann, D
Stenmark-Askmalm, M
Stoppa-Lyonnet, D
Swerdlow, A
Szabo, CI
Tamimi, R
Tapper, W
Teixeira, MR
Teo, SH
Terry, MB
Thomassen, M
Thompson, D
Tihomirova, L
Toland, AE
Tollenaar, RAEM
Tomlinson, I
Truong, T
Tsimiklis, H
Teule, A
Tumino, R
Tung, N
Turnbull, C
Ursin, G
van Deurzen, CHM
van Rensburg, EJ
Varon-Mateeva, R
Wang, ZM
Wang-Gohrke, S
Weiderpass, E
Weitzel, JN
Whittemore, A
Wildiers, H
Winqvist, R
Yang, XHR
Yannoukakos, D
Yao, S
Zamora, MP
Zheng, W
Hall, P
Kraft, P
Vachon, C
Slager, S
Chenevix-Trench, G
Pharoah, PDP
Monteiro, AAN
Garcia-Closas, M
Easton, DF
Antoniou, AC
AF Couch, Fergus J.
Kuchenbaecker, Karoline B.
Michailidou, Kyriaki
Mendoza-Fandino, Gustavo A.
Nord, Silje
Lilyquist, Janna
Olswold, Curtis
Hallberg, Emily
Agata, Simona
Ahsan, Habibul
Aittomaeki, Kristiina
Ambrosone, Christine
Andrulis, Irene L.
Anton-Culver, Hoda
Arndt, Volker
Arun, Banu K.
Arver, Brita
Barile, Monica
Barkardottir, Rosa B.
Barrowdale, Daniel
Beckmann, Lars
Beckmann, Matthias W.
Benitez, Javier
Blank, Stephanie V.
Blomqvist, Carl
Bogdanova, Natalia V.
Bojesen, Stig E.
Bolla, Manjeet K.
Bonanni, Bernardo
Brauch, Hiltrud
Brenner, Hermann
Burwinkel, Barbara
Buys, Saundra S.
Caldes, Trinidad
Caligo, Maria A.
Canzian, Federico
Carpenter, Jane
Chang-Claude, Jenny
Chanock, Stephen J.
Chung, Wendy K.
Claes, Kathleen B. M.
Cox, Angela
Cross, Simon S.
Cunningham, Julie M.
Czene, Kamila
Daly, Mary B.
Damiola, Francesca
Darabi, Hatef
de la Hoya, Miguel
Devilee, Peter
Diez, Orland
Ding, Yuan C.
Dolcetti, Riccardo
Domchek, Susan M.
Dorfling, Cecilia M.
dos-Santos-Silva, Isabel
Dumont, Martine
Dunning, Alison M.
Eccles, Diana M.
Ehrencrona, Hans
Ekici, Arif B.
Eliassen, Heather
Ellis, Steve
Fasching, Peter A.
Figueroa, Jonine
Flesch-Janys, Dieter
Foersti, Asta
Fostira, Florentia
Foulkes, William D.
Friebel, Tara
Friedman, Eitan
Frost, Debra
Gabrielson, Marike
Gammon, Marilie D.
Ganz, Patricia A.
Gapstur, Susan M.
Garber, Judy
Gaudet, Mia M.
Gayther, Simon A.
Gerdes, Anne-Marie
Ghoussaini, Maya
Giles, Graham G.
Glendon, Gord
Godwin, Andrew K.
Goldberg, Mark S.
Goldgar, David E.
Gonzalez-Neira, Anna
Greene, Mark H.
Gronwald, Jacek
Guenel, Pascal
Gunter, Marc
Haeberle, Lothar
Haiman, Christopher A.
Hamann, Ute
Hansen, Thomas V. O.
Hart, Steven
Healey, Sue
Heikkinen, Tuomas
Henderson, Brian E.
Herzog, Josef
Hogervorst, Frans B. L.
Hollestelle, Antoinette
Hooning, Maartje J.
Hoover, Robert N.
Hopper, John L.
Humphreys, Keith
Hunter, David J.
Huzarski, Tomasz
Imyanitov, Evgeny N.
Isaacs, Claudine
Jakubowska, Anna
James, Paul
Janavicius, Ramunas
Jensen, Uffe Birk
John, Esther M.
Jones, Michael
Kabisch, Maria
Kar, Siddhartha
Karlan, Beth Y.
Khan, Sofia
Khaw, Kay-Tee
Kibriya, Muhammad G.
Knight, Julia A.
Ko, Yon-Dschun
Konstantopoulou, Irene
Kosma, Veli-Matti
Kristensen, Vessela
Kwong, Ava
Laitman, Yael
Lambrechts, Diether
Lazaro, Conxi
Lee, Eunjung
Le Marchand, Loic
Lester, Jenny
Lindblom, Annika
Lindor, Noralane
Lindstrom, Sara
Liu, Jianjun
Long, Jirong
Lubinski, Jan
Mai, Phuong L.
Makalic, Enes
Malone, Kathleen E.
Mannermaa, Arto
Manoukian, Siranoush
Margolin, Sara
Marme, Frederik
Martens, John W. M.
McGuffog, Lesley
Meindl, Alfons
Miller, Austin
Milne, Roger L.
Miron, Penelope
Montagna, Marco
Mazoyer, Sylvie
Mulligan, Anna M.
Muranen, Taru A.
Nathanson, Katherine L.
Neuhausen, Susan L.
Nevanlinna, Heli
Nordestgaard, Borge G.
Nussbaum, Robert L.
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I.
Olson, Janet E.
Osorio, Ana
Park, Sue K.
Peeters, Petra H.
Peissel, Bernard
Peterlongo, Paolo
Peto, Julian
Phelan, Catherine M.
Pilarski, Robert
Poppe, Bruce
Pylkaes, Katri
Radice, Paolo
Rahman, Nazneen
Rantala, Johanna
Rappaport, Christine
Rennert, Gad
Richardson, Andrea
Robson, Mark
Romieu, Isabelle
Rudolph, Anja
Rutgers, Emiel J.
Sanchez, Maria-Jose
Santella, Regina M.
Sawyer, Elinor J.
Schmidt, Daniel F.
Schmidt, Marjanka K.
Schmutzler, Rita K.
Schumacher, Fredrick
Scott, Rodney
Senter, Leigha
Sharma, Priyanka
Simard, Jacques
Singer, Christian F.
Sinilnikova, Olga M.
Soucy, Penny
Southey, Melissa
Steinemann, Doris
Stenmark-Askmalm, Marie
Stoppa-Lyonnet, Dominique
Swerdlow, Anthony
Szabo, Csilla I.
Tamimi, Rulla
Tapper, William
Teixeira, Manuel R.
Teo, Soo-Hwang
Terry, Mary B.
Thomassen, Mads
Thompson, Deborah
Tihomirova, Laima
Toland, Amanda E.
Tollenaar, Robert A. E. M.
Tomlinson, Ian
Truong, Therese
Tsimiklis, Helen
Teule, Alex
Tumino, Rosario
Tung, Nadine
Turnbull, Clare
Ursin, Giski
van Deurzen, Carolien H. M.
van Rensburg, Elizabeth J.
Varon-Mateeva, Raymonda
Wang, Zhaoming
Wang-Gohrke, Shan
Weiderpass, Elisabete
Weitzel, Jeffrey N.
Whittemore, Alice
Wildiers, Hans
Winqvist, Robert
Yang, Xiaohong R.
Yannoukakos, Drakoulis
Yao, Song
Zamora, M. Pilar
Zheng, Wei
Hall, Per
Kraft, Peter
Vachon, Celine
Slager, Susan
Chenevix-Trench, Georgia
Pharoah, Paul D. P.
Monteiro, Alvaro A. N.
Garcia-Closas, Montserrat
Easton, Douglas F.
Antoniou, Antonis C.
TI Identification of four novel susceptibility loci for oestrogen receptor
negative breast cancer
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; PANCREATIC-CANCER;
COMMON VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; TELOMERE
LENGTH; RISK; METAANALYSIS; IDENTIFY
AB Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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[Whittemore, Alice] Stanford Univ, Sch Med, Dept Hlth Res Policy Epidemiol, Stanford, CA 94305 USA.
[Wildiers, Hans] Univ Hosp, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, B-3000 Leuven, Belgium.
[Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Zamora, M. Pilar] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia.
[Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.; Couch, FJ (reprint author), Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
EM couch.fergus@mayo.edu
RI Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Osorio,
Ana/I-4324-2014; Weiderpass, Elisabete/M-4029-2016; Teo,
Soo-hwang/H-2353-2014; Knight, Julia/A-6843-2012; Zheng,
Wei/O-3351-2013; Nord, Silje/R-5212-2016; Gronwald, Jacek/A-4576-2017;
Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017; montagna, marco/E-2225-2012
OI Ehrencrona, Hans/0000-0002-5589-3622; Khan, Sofia/0000-0003-4185-8882;
Muranen, Taru/0000-0002-5895-1808; Yannoukakos,
Drakoulis/0000-0001-7509-3510; Dunning, Alison
Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099;
Dolcetti, Riccardo/0000-0003-1625-9853; Osorio, Ana/0000-0001-8124-3984;
Weiderpass, Elisabete/0000-0003-2237-0128; Zheng,
Wei/0000-0003-1226-070X; Nord, Silje/0000-0002-3271-5356; Gronwald,
Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572;
manoukian, siranoush/0000-0002-6034-7562; Peissel,
Bernard/0000-0001-9233-3571; montagna, marco/0000-0002-4929-2150
FU European Community Seventh Framework Programme [223175,
HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C12292/A11174];
National Institutes of Health [CA116201, CA128978, CA176785, CA192393];
National Institutes of Health, Post-Cancer GWAS initiative [1U19
CA148537, 1U19 CA148065, 1U19 CA148112]; National Institutes of Health,
GAME-ON initiative; Canadian Institutes of Health Research (CIHR);
Breast Cancer Res. Foundation; Ovarian Cancer Research Fund; Department
of Defence [W81XWH-10-1-0341]; Florida Breast Cancer Foundation
FX B.C.A.C. was funded through a European Community Seventh Framework
Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS);
Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National
Institutes of Health Specialized Program of Research Excellence (SPORE)
in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393),
and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19
CA148112 - the GAME-ON initiative); the Canadian Institutes of Health
Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer,
the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund.
CIMBA genotyping was supported by National Institutes of Health grant
(CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast
Cancer Res. Foundation. CIMBA data management and data analysis were
supported by Cancer Research UK grants C12292/A11174 and C1287/A10118.
This study made use of data generated by the Wellcome Trust Case Control
consortium. Functional studies were supported by the Florida Breast
Cancer Foundation. A full description of funding and acknowledgments is
provided in Supplementary Note 1.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 11375
DI 10.1038/ncomms11375
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK4NF
UT WOS:000374894400001
PM 27117709
ER
PT J
AU Freedman, JE
Gerstein, M
Mick, E
Rozowsky, J
Levy, D
Kitchen, R
Das, S
Shah, R
Danielson, K
Beaulieu, L
Navarro, FCP
Wang, YY
Galeev, TR
Holman, A
Kwong, RY
Murthy, V
Tanriverdi, SE
Koupenova-Zamor, M
Mikhalev, E
Tanriverdi, K
AF Freedman, Jane E.
Gerstein, Mark
Mick, Eric
Rozowsky, Joel
Levy, Daniel
Kitchen, Robert
Das, Saumya
Shah, Ravi
Danielson, Kirsty
Beaulieu, Lea
Navarro, Fabio C. P.
Wang, Yaoyu
Galeev, Timur R.
Holman, Alex
Kwong, Raymond Y.
Murthy, Venkatesh
Tanriverdi, Selim E.
Koupenova-Zamor, Milka
Mikhalev, Ekaterina
Tanriverdi, Kahraman
TI Diverse human extracellular RNAs are widely detected in human plasma
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SEQUENCING EXPERIMENTS; CIRCULATING MICRORNAS; SMALL NUCLEOLAR;
C-ELEGANS; EXPRESSION; BIOMARKERS; PLATELET; DATABASE; BLOOD;
TRANSCRIPTOME
AB There is growing appreciation for the importance of non-protein-coding genes in development and disease. Although much is known about microRNAs, limitations in bioinformatic analyses of RNA sequencing have precluded broad assessment of other forms of small-RNAs in humans. By analysing sequencing data from plasma-derived RNA from 40 individuals, here we identified over a thousand human extracellular RNAs including microRNAs, piwi-interacting RNA (piRNA), and small nucleolar RNAs. Using a targeted quantitative PCR with reverse transcription approach in an additional 2,763 individuals, we characterized almost 500 of the most abundant extracellular transcripts including microRNAs, piRNAs and small nucleolar RNAs. The presence in plasma of many non-microRNA small-RNAs was confirmed in an independent cohort. We present comprehensive data to demonstrate the broad and consistent detection of diverse classes of circulating non-cellular small-RNAs from a large population.
C1 [Freedman, Jane E.; Beaulieu, Lea; Tanriverdi, Selim E.; Koupenova-Zamor, Milka; Mikhalev, Ekaterina; Tanriverdi, Kahraman] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA.
[Gerstein, Mark; Rozowsky, Joel; Kitchen, Robert; Navarro, Fabio C. P.; Galeev, Timur R.] Yale Univ, Sch Med, Computat Biol & Bioinformat Program, 333 Cedar St, New Haven, CT 06520 USA.
[Mick, Eric] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA.
[Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
[Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20824 USA.
[Das, Saumya; Shah, Ravi; Danielson, Kirsty] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Wang, Yaoyu; Holman, Alex] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
[Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
[Murthy, Venkatesh] Univ Michigan, Ann Arbor, MI 48409 USA.
RP Freedman, JE (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01605 USA.
EM jane.freedman@umassmed.edu
OI Navarro, Fabio/0000-0002-5640-9070; Murthy,
Venkatesh/0000-0002-7901-1321; Rozowsky, Joel/0000-0002-3565-0762
FU NIH Common Fund, through the Office of Strategic Coordination/Office of
the NIH Director [N01-HC 25195, P01-HL085381, UH2TR000921, U01HL126495,
UH2TR000901]
FX This work was supported by N01-HC 25195, P01-HL085381 (to J.E.F.);
UH2TR000921, U01HL126495 (to J.E.F.); and UH2TR000901 (to S.D.), that
are supported by the NIH Common Fund, through the Office of Strategic
Coordination/Office of the NIH Director. We thank Lillian Kuo, Danilo
Tagle and Pothur Srinivas of the NIH Common Fund for their assistance
and guidance.
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PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 11106
DI 10.1038/ncomms11106
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK4MK
UT WOS:000374892300001
PM 27112789
ER
PT J
AU Jiang, X
Hu, C
Arnovitz, S
Bugno, J
Yu, M
Zuo, ZX
Chen, P
Huang, H
Ulrich, B
Gurbuxani, S
Weng, HY
Strong, J
Wang, YG
Li, YY
Salat, J
Li, SL
Elkahloun, AG
Yang, Y
Neilly, MB
Larson, RA
Le Beau, MM
Herold, T
Bohlander, SK
Liu, PP
Zhang, JW
Li, ZJ
He, C
Jin, J
Hong, S
Chen, JJ
AF Jiang, Xi
Hu, Chao
Arnovitz, Stephen
Bugno, Jason
Yu, Miao
Zuo, Zhixiang
Chen, Ping
Huang, Hao
Ulrich, Bryan
Gurbuxani, Sandeep
Weng, Hengyou
Strong, Jennifer
Wang, Yungui
Li, Yuanyuan
Salat, Justin
Li, Shenglai
Elkahloun, Abdel G.
Yang, Yang
Neilly, Mary Beth
Larson, Richard A.
Le Beau, Michelle M.
Herold, Tobias
Bohlander, Stefan K.
Liu, Paul P.
Zhang, Jiwang
Li, Zejuan
He, Chuan
Jin, Jie
Hong, Seungpyo
Chen, Jianjun
TI miR-22 has a potent anti-tumour role with therapeutic potential in acute
myeloid leukaemia
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; CELL SELF-RENEWAL; STEM-CELLS;
MYELODYSPLASTIC SYNDROMES; TUMOR-SUPPRESSOR; DELETED REGION;
TRANSFORMATION; MLL; TARGETS; TET2
AB MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy.
C1 [Jiang, Xi; Hu, Chao; Zuo, Zhixiang; Weng, Hengyou; Strong, Jennifer; Wang, Yungui; Chen, Jianjun] Univ Cincinnati, Dept Canc Biol, Cincinnati, OH 45219 USA.
[Jiang, Xi; Hu, Chao; Arnovitz, Stephen; Zuo, Zhixiang; Chen, Ping; Huang, Hao; Ulrich, Bryan; Weng, Hengyou; Wang, Yungui; Li, Yuanyuan; Salat, Justin; Li, Shenglai; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Li, Zejuan; Chen, Jianjun] Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA.
[Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Dept Hematol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China.
[Bugno, Jason; Yang, Yang; Hong, Seungpyo] Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL 60612 USA.
[Yu, Miao; He, Chuan] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA.
[Yu, Miao; He, Chuan] Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Zuo, Zhixiang] Sun Yat Sen Univ, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
[Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Elkahloun, Abdel G.; Liu, Paul P.] NHGRI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Herold, Tobias] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, D-81377 Munich, Germany.
[Bohlander, Stefan K.] Univ Auckland, Dept Mol Med & Pathol, Auckland 1142, New Zealand.
[Zhang, Jiwang] Loyola Univ, Med Ctr, Inst Oncol, Cardinal Bernardin Canc Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA.
[Li, Zejuan] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Hong, Seungpyo] Yonsei Univ, Integrated Sci & Engn Div, Underwood Int Coll, Inchon 406840, South Korea.
RP Chen, JJ (reprint author), Univ Cincinnati, Dept Canc Biol, Cincinnati, OH 45219 USA.; Chen, JJ (reprint author), Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA.
EM chen3jj@ucmail.uc.edu
RI Zuo, Zhixiang/M-4441-2016;
OI Zuo, Zhixiang/0000-0002-2492-2689; Herold, Tobias/0000-0002-9615-9432;
Larson, Richard/0000-0001-9168-3203
FU Leukemia & Lymphoma Society (LLS) Translational Research Grant; National
Institutes of Health (NIH) R01 Grant [CA178454, CA182528, CA127277];
American Cancer Society (ACS) Research Scholar grant; University of
Chicago Committee on Cancer Biology (CCB) Fellowship Program; LLS
Special Fellowship; Gabrielle's Angel Foundation for Cancer Research;
Intramural Research Program of National Human Genome Research Institute,
NIH
FX Special thanks to the late Dr Janet Rowley for her long-term support. We
also thank Drs Pier P. Pandolfi, Sheena Josselyn, Dong-Er Zhang, Scott
Armstrong, Michael Cleary, James Mulloy, Robert Slany, Lin He and
Michael Thirman for providing mouse models, retroviral constructs or
cell lines, and the German AMLCG study group for AML microarray data.
This work was supported by Leukemia & Lymphoma Society (LLS)
Translational Research Grant (J.C.), the National Institutes of Health
(NIH) R01 Grants CA178454, CA182528 and CA127277 (J.C.), American Cancer
Society (ACS) Research Scholar grant (J.C.), The University of Chicago
Committee on Cancer Biology (CCB) Fellowship Program (X.J.), LLS Special
Fellowship (Z.L.), Gabrielle's Angel Foundation for Cancer Research
(J.C., Z.L., X.J. and H.H.) and Intramural Research Program of National
Human Genome Research Institute, NIH (A.G.E. and P.P.L.). C.H. is an
investigator of the Howard Hughes Medical Institute.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 11452
DI 10.1038/ncomms11452
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK4NU
UT WOS:000374896000001
PM 27116251
ER
PT J
AU Leusink, M
Maitland-van der Zee, AH
Ding, B
Drenos, F
van Iperen, EPA
Warren, HR
Caulfield, MJ
Cupples, LA
Cushman, M
Hingorani, AD
Hoogeveen, RC
Hovingh, GK
Kumari, M
Lange, LA
Munroe, PB
Nyberg, F
Schreiner, PJ
Sivapalaratnam, S
de Bakker, PIW
de Boer, A
Keating, BJ
Asselbergs, FW
Onland-Moret, NC
AF Leusink, Maarten
Maitland-van der Zee, Anke H.
Ding, Bo
Drenos, Fotios
van Iperen, Erik P. A.
Warren, Helen R.
Caulfield, Mark J.
Cupples, L. Adrienne
Cushman, Mary
Hingorani, Aroon D.
Hoogeveen, Ron C.
Hovingh, G. Kees
Kumari, Meena
Lange, Leslie A.
Munroe, Patricia B.
Nyberg, Fredrik
Schreiner, Pamela J.
Sivapalaratnam, Suthesh
de Bakker, Paul I. W.
de Boer, Anthonius
Keating, Brendan J.
Asselbergs, Folkert W.
Onland-Moret, N. Charlotte
TI A genetic risk score is associated with statin-induced low-density
lipoprotein cholesterol lowering
SO PHARMACOGENOMICS
LA English
DT Article
DE pharmacogenetics cholesterol; risk score; statin therapy
ID GENOME-WIDE ASSOCIATION; CENTRIC METAANALYSIS; RANDOMIZED-TRIALS; LDL
CHOLESTEROL; THERAPY; LOCI; REDUCTION; VARIANTS; DISEASE; ROSUVASTATIN
AB Aim: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. Patients & methods: In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 x 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE. Results: No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 x 10(-4)). Conclusion: The GRS was associated with statin response, but the small effect size (similar to 2% of the average low-density lipoprotein cholesterol reduction) limits applicability.
C1 [Leusink, Maarten; de Bakker, Paul I. W.; Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Leusink, Maarten; Maitland-van der Zee, Anke H.; de Boer, Anthonius] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Fac Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
[Ding, Bo; Nyberg, Fredrik] AstraZeneca R&D Gothenburg, Global Med Affairs, Med Evidence & Observat Res Ctr, Molndal, Sweden.
[Drenos, Fotios] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.
[Drenos, Fotios] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England.
[van Iperen, Erik P. A.; Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
[van Iperen, Erik P. A.] Acad Med Ctr Amsterdam, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands.
[Warren, Helen R.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London, England.
[Warren, Helen R.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Hingorani, Aroon D.] UCL, Dept Epidemiol & Publ Hlth, UCL Inst Epidemiol & Hlth Care, London, England.
[Hoogeveen, Ron C.] Baylor Coll Med, Dept Med, Div Atherosclerosis & Vasc Med, Houston, TX 77030 USA.
[Hovingh, G. Kees; Sivapalaratnam, Suthesh] Acad Med Ctr Amsterdam, Dept Vasc Med, Amsterdam, Netherlands.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Sch Med Chapel Hill, Chapel Hill, NC USA.
[Nyberg, Fredrik] Univ Gothenburg, Dept Publ Hlth & Community Med, Sahlgrenska Acad, Occupat & Environm Med,Inst Med, Gothenburg, Sweden.
[Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Keating, Brendan J.] Hosp Univ Penn, Dept Surg, Div Transplantat, 3400 Spruce St, Philadelphia, PA 19104 USA.
[Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
[Asselbergs, Folkert W.] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
RP Onland-Moret, NC (reprint author), Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
EM N.C.Onland@umcutrecht.nl
RI Onland-Moret, N. Charlotte/G-9185-2011;
OI Kumari, Meena/0000-0001-9716-1035
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HH-SN268201100006C, HHSN268201100007C, HHSN26820-1100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human
Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C,
N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321]; National
Institutes of Health [UL1RR025005]; Pfizer, NY, USA; Leo Laboratories,
Copenhagen, Denmark; National Heart, Lung and Blood Institute; NHLBI
[HHSN268200960009C]; NIH Intramural Research Program; AstraZeneca;
University of Washington [N01-HC-95159]; University of California, Los
Angeles [N01-HC-95160]; Columbia University [N01-HC-95161]; Johns
Hopkins University [N01-HC-95162, N01-HC-95168]; University of Minnesota
[N01-HC-95163]; Northwestern University [N01-HC-95164]; Wake Forest
University [N01-HC-95165]; University of Vermont [N01-HC-95166]; New
England Medical Center [N01-HC-95167]; Harbor-UCLA Research and
Education Institute [N01-HC-95169]; Cedars-Sinai Medical Center
[R01-HL-071205]; University of Virginia; Medical Research Council;
British Heart Foundation; Health and Safety Executive; Department of
Health; National Heart Lung and Blood Institute [HL36310]; US, NIH:
National Institute on Aging [AG13196]; US, NIH [HS06516]; John D and
Catherine T MacArthur Foundation Research Networks on Successful Midlife
Development and Socio-economic Status and Health; Netherlands
Organisation for Health Research and Development (ZonMw grant)
[90700342]; Utrecht University ('Epidemiology - Program'); NIH Roadmap
for Medical Research; Agency for Health Care Policy Research
FX This work was supported by: ARIC: The Athero-sclerosis Risk in
Communities Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute contracts (HHSN268201100005C,
HH-SN268201100006C, HHSN268201100007C, HHSN26820-1100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and
HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National
Human Genome Research Institute contract U01HG004402; and NIH contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research; ASCOT: This
work was supported by Pfizer, NY, USA, for the ASCOT study and the
collection of the ASCOT DNA repository; by Servier Research Group,
Paris, France; and by Leo Laboratories, Copenhagen, Denmark. We thank
all ASCOT trial participants, physicians, nurses and practices in the
participating countries for their important contribution to the study.
We thank the Centre National de Genotypage for genotyping. This work
forms part of the research themes contributing to the translational
research portfolio for the NIHR Barts Cardiovascular Biomedical Research
Unit (Warren, Munroe and Caulfield); CARe: wishes to acknowledge the
support of the National Heart, Lung and Blood Institute and the
contributions of the research institutions, study investigators, field
staff, and study participants in creating this resource for biomedical
research (NHLBI contract number HHSN268200960009C); FHS: The Framingham
Heart Study research included in this study is funded by NIH
grant/contract N01-HC-25195, R01-HL-092577, R01-HL-076784,
R01-AG-028321, and by the NIH Intramural Research Program; JUPITER: The
Jupiter study and genotyping of the study participants was funded by
AstraZeneca; MESA: MESA was supported by the following: University of
Washington (N01-HC-95159), University of California, Los Angeles
(N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins
University (N01-HC-95162, N01-HC-95168), University of Minnesota
(N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest
University (N01-HC-95165), University of Vermont (N01-HC-95166), New
England Medical Center (N01-HC-95167), Harbor-UCLA Research and
Education Institute (N01-HC-95169), Cedars-Sinai Medical Center
(R01-HL-071205) and University of Virginia. The authors thank the other
investigators, the staff, and the participants of the MESA study for
their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
http://www.mesa-nhlbi.org; WHII: We thank all participating women and
men in the Whitehall II Study, as well as all Whitehall II research
scientists, study and data managers and clinical and administrative
staff who make the study possible. The Whitehall II study has been
supported by grants from the Medical Research Council; British Heart
Foundation; Health and Safety Executive; Department of Health; National
Heart Lung and Blood Institute (HL36310), US, NIH: National Institute on
Aging (AG13196), US, NIH; Agency for Health Care Policy Research
(HS06516); and the John D and Catherine T MacArthur Foundation Research
Networks on Successful Midlife Development and Socio-economic Status and
Health. AD Hingorani holds a British Heart Foundation Senior Research -
Fellowship.; A clinical fellowship from The Netherlands Organisation for
Health Research and Development (ZonMw grant 90700342 to FW Asselbergs);
Utrecht University ('Epidemiology - Program' to M Leusink). The authors
have no other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 29
TC 1
Z9 1
U1 1
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1462-2416
EI 1744-8042
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD APR
PY 2016
VL 17
IS 6
BP 583
EP 591
DI 10.2217/pgs.16.8
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK8AG
UT WOS:000375148200007
PM 27045730
ER
PT J
AU Bonfrate, A
Farah, J
De Marzi, L
Delacroix, S
Herault, J
Sayah, R
Lee, C
Bolch, WE
Clairand, I
AF Bonfrate, A.
Farah, J.
De Marzi, L.
Delacroix, S.
Herault, J.
Sayah, R.
Lee, C.
Bolch, W. E.
Clairand, I.
TI Influence of beam incidence and irradiation parameters on stray neutron
doses to healthy organs of pediatric patients treated for an
intracranial tumor with passive scattering proton therapy
SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS
LA English
DT Article
DE Proton therapy; Stray neutron doses; Intracranial treatments; Beam
incidence
ID ACCELERATOR-DRIVEN SYSTEMS; MONTE-CARLO; 2ND CANCER; EQUIVALENT;
RADIATION; PHANTOMS; RISK; RADIOTHERAPY; EXPOSURES; DOSIMETRY
AB Purpose: In scattering proton therapy, the beam incidence, i.e. the patient's orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature.
Methods: MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size.
Results: Using a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63 mu Gy Gy(-1) and 149 mu Gy Gy(-1) were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient's orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5 times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence.
Conclusion: Beam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
C1 [Bonfrate, A.; Farah, J.; Sayah, R.; Clairand, I.] IRSN Inst Radioprotect & Surete Nucl, Serv Dosimetrie Externe, BP17, F-92262 Fontenay Aux Roses, France.
[De Marzi, L.; Delacroix, S.] Inst Curie, Ctr Protontherapie Orsay CPO, Campus Univ Batiment 101, F-91898 Orsay, France.
[Herault, J.] Ctr Antoine Lacassagne CAL Cyclotron Biomed, 227 Ave Lanterne, F-06200 Nice, France.
[Lee, C.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Bolch, W. E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
RP Bonfrate, A; Farah, J (reprint author), IRSN Inst Radioprotect & Surete Nucl, Serv Dosimetrie Externe, BP17, F-92262 Fontenay Aux Roses, France.
EM anthony.bonfrate@irsn.fr; jad.farah@irsn.fr
NR 38
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U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1120-1797
EI 1724-191X
J9 PHYS MEDICA
JI Phys. Medica
PD APR
PY 2016
VL 32
IS 4
BP 590
EP 599
DI 10.1016/j.ejmp.2016.03.009
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK7SK
UT WOS:000375125800008
PM 27050170
ER
PT J
AU Bai, L
Yang, HH
Hu, Y
Shukla, A
Ha, NH
Doran, A
Faraji, F
Goldberger, N
Lee, MP
Keane, T
Hunter, KW
AF Bai, Ling
Yang, Howard H.
Hu, Ying
Shukla, Anjali
Ngoc-Han Ha
Doran, Anthony
Faraji, Farhoud
Goldberger, Natalie
Lee, Maxwell P.
Keane, Thomas
Hunter, Kent W.
TI An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer
Metastasis Susceptibility Genes
SO PLOS GENETICS
LA English
DT Article
ID MAMMARY-TUMORS; PROGRESSION; EXPRESSION; METFORMIN; PROGNOSIS;
IDENTIFICATION; ARCHITECTURE; SIGNATURE; MODIFIERS; SURVIVAL
AB Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.
C1 [Bai, Ling; Yang, Howard H.; Shukla, Anjali; Ngoc-Han Ha; Faraji, Farhoud; Goldberger, Natalie; Lee, Maxwell P.; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Hu, Ying] NCI, Ctr Bioinformat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Doran, Anthony; Keane, Thomas] Welcome Trust Sanger Ctr, Computat Genom Program, Cambridge, England.
RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
EM hunterk@mail.nih.gov
OI Doran, Anthony/0000-0003-3061-4102; Faraji, Farhoud/0000-0001-5078-813X
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
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Z9 2
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD APR
PY 2016
VL 12
IS 4
AR e1005989
DI 10.1371/journal.pgen.1005989
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA DK9DW
UT WOS:000375231900035
PM 27074153
ER
PT J
AU Santiago, PB
Assumpcao, TCF
de Araujo, CN
Bastos, IMD
Neves, D
da Silva, IG
Charneau, S
Queiroz, RML
Raiol, T
Oliveira, JVD
de Sousa, MV
Calvo, E
Ribeiro, JMC
Santana, JM
AF Santiago, Paula Beatriz
Assumpcao, Teresa C. F.
de Araujo, Carla Nunes
Dourado Bastos, Izabela Marques
Neves, David
da Silva, Ionizete Garcia
Charneau, Sebastien
Queiroz, Rayner Myr L.
Raiol, Taina
de Araujo Oliveira, Joao Victor
de Sousa, Marcelo Valle
Calvo, Eric
Ribeiro, Jose M. C.
Santana, Jaime M.
TI A Deep Insight into the Sialome of Rhodnius neglectus, a Vector of
Chagas Disease
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID SNAKE-VENOM METALLOPROTEINASE; PHEROMONE-BINDING-PROTEIN; BLOOD-FEEDING
ARTHROPODS; KAZAL-TYPE INHIBITOR; TICK IXODES-RICINUS;
PLATELET-AGGREGATION; THROMBIN INHIBITOR; TRIATOMA-INFESTANS;
SERINE-PROTEASE; SALIVARY-GLANDS
AB Background
Triatomines are hematophagous insects that act as vectors of Chagas disease. Rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this American trypanosomiasis. The saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immune responses.
Methods/Principal
Findings Next generation sequencing and mass spectrometry-based protein identification were performed to investigate the content of triatomine R. neglectus saliva. We deposited 4,230 coding DNA sequences (CDS) in GenBank. A set of 636 CDS of proteins of putative secretory nature was extracted from the assembled reads, 73 of them confirmed by proteomic analysis. The sialome of R. neglectus was characterized and serine protease transcripts detected. The presence of ubiquitous protein families was revealed, including lipocalins, serine protease inhibitors, and antigen-5. Metalloproteases, disintegrins, and odorant binding protein families were less abundant.
Conclusions/Significance
The data presented improve our understanding of hematophagous arthropod sialomes, and aid in understanding hematophagy and the complex interplay among vectors and their vertebrate hosts.
C1 [Santiago, Paula Beatriz; Assumpcao, Teresa C. F.; de Araujo, Carla Nunes; Dourado Bastos, Izabela Marques; Neves, David; Charneau, Sebastien; Queiroz, Rayner Myr L.; Raiol, Taina; de Sousa, Marcelo Valle; Santana, Jaime M.] Univ Brasilia, Dept Cell Biol, Brasilia, DF, Brazil.
[Assumpcao, Teresa C. F.; Calvo, Eric; Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, Rockville, MD USA.
[de Araujo, Carla Nunes] Univ Brasilia, Ceilandia Fac, Brasilia, DF, Brazil.
[da Silva, Ionizete Garcia] Univ Goias, Dept Parasitol, Jatai, Brazil.
[Raiol, Taina] Inst Leonidas & Maria Deane Fiocruz Amazonia, Manaus, Amazonas, Brazil.
[de Araujo Oliveira, Joao Victor] Univ Brasilia, Dept Comp Sci, Brasilia, DF, Brazil.
RP Santana, JM (reprint author), Univ Brasilia, Dept Cell Biol, Brasilia, DF, Brazil.
EM jsantana@unb.br
OI Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818
FU Brazilian National Council for Scientific and Technological Development
(CNPq) [476252/2012-1]; PROAP from the Coordenacao de Aperfeicoamento de
Pessoal de Nivel Superior (CAPES); CT-Infra from the Financiadora de
Estudos e Projetos (Finep); Fundacao de Apoio a Pesquisa do Distrito
Federal (FAPDF) [Pronex 476252/2012-5]; National Institute of Allergy
and Infectious Diseases (NIAID); [Z01 AI000810-18]
FX This work was supported by grants 476252/2012-1 (http://www.cnpq.br)
from the Brazilian National Council for Scientific and Technological
Development (CNPq), PROAP-2013 (http://www.capes.gov.br) from the
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES),
CT-Infra 2011 (http://www.finep.gov.br) from the Financiadora de Estudos
e Projetos (Finep), and Pronex 476252/2012-5 (http://www.fap.df.gov.br)
from the Fundacao de Apoio a Pesquisa do Distrito Federal (FAPDF) to
JMS; and Z01 AI000810-18 (http://www.niaid.nih.gov/Pages/default.aspx)
to Vector-Borne Diseases: Biology of Vector Host Relationship, from the
National Institute of Allergy and Infectious Diseases (NIAID) to JMCR.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 107
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Z9 2
U1 4
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD APR
PY 2016
VL 10
IS 4
AR e0004581
DI 10.1371/journal.pntd.0004581
PG 25
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DL1FC
UT WOS:000375376700028
PM 27129103
ER
PT J
AU Schioler, KL
Alifrangis, M
Kitron, U
Konradsen, F
AF Schioler, Karin L.
Alifrangis, Michael
Kitron, Uriel
Konradsen, Flemming
TI Insecticidal Paints: A Realistic Approach to Vector Control?
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DELTAMETHRIN; POPULATIONS; MORTALITY; NETS
C1 [Schioler, Karin L.; Konradsen, Flemming] Univ Copenhagen, Dept Publ Hlth, Global Hlth Sect, Copenhagen, Denmark.
[Alifrangis, Michael] Univ Copenhagen, Dept Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark.
[Alifrangis, Michael] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen, Denmark.
[Kitron, Uriel] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.
[Kitron, Uriel] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Schioler, KL (reprint author), Univ Copenhagen, Dept Publ Hlth, Global Hlth Sect, Copenhagen, Denmark.
EM ksch@sund.ku.dk
NR 14
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD APR
PY 2016
VL 10
IS 4
AR e0004518
DI 10.1371/journal.pntd.0004518
PG 5
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DL1FC
UT WOS:000375376700013
PM 27101473
ER
PT J
AU Treangen, TJ
Schoeler, G
Phillippy, AM
Bergman, NH
Turell, MJ
AF Treangen, Todd J.
Schoeler, George
Phillippy, Adam M.
Bergman, Nicholas H.
Turell, Michael J.
TI Identification and Genomic Analysis of a Novel Group C Orthobunyavirus
Isolated from a Mosquito Captured near Iquitos, Peru
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID AEDES-ALBOPICTUS; DIPTERA-CULICIDAE; UNITED-STATES; SINGLE-CELL; VIRUS;
SEQUENCES; ALIGNMENT; VALLEY; BUNYAVIRUSES; TRANSMISSION
AB Group C orthobunyaviruses are single-stranded RNA viruses found in both South and North America. Until very recently, and despite their status as important vector-borne human pathogens, no Group C whole genome sequences containing all three segments were available in public databases. Here we report a Group C orthobunyavirus, named El Huayo virus, isolated from a pool of Culex portesi mosquitoes captured near Iquitos, Peru. Although initial metagenomic analysis yielded only a handful of reads belonging to the genus Orthobunyavirus, single contig assemblies were generated for L, M, and S segments totaling over 200,000 reads (similar to 0.5% of sample). Given the moderately high viremia in hamsters (>10(7) plaque-forming units/ml) and the propensity for Cx. portesi to feed on rodents, it is possible that El Huayo virus is maintained in nature in a Culex portesi/rodent cycle. El Huayo virus was found to be most similar to Peruvian Caraparu virus isolates and constitutes a novel sub-clade within Group C.
C1 [Treangen, Todd J.; Phillippy, Adam M.; Bergman, Nicholas H.] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA.
[Schoeler, George] US Naval Med Res Unit 6, Dept Entomol, Callao, Peru.
[Turell, Michael J.] US Army, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA.
[Schoeler, George] Bur Med & Surg, Falls Church, VA USA.
[Phillippy, Adam M.] NHGRI, Genome Informat Sect, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Treangen, TJ (reprint author), Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA.
EM treangent@nbacc.net
FU Department of Homeland Security (DHS) Science and Technology Directorate
(ST) [HSHQDC-07-C-00020]; Federally Funded Research and Development
Center
FX This work was funded under Agreement No. HSHQDC-07-C-00020 awarded by
the Department of Homeland Security (DHS) Science and Technology
Directorate (S&T) for the management and operation of the National
Biodefense Analysis and Countermeasures Center (NBACC), a Federally
Funded Research and Development Center. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
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U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD APR
PY 2016
VL 10
IS 4
AR e0004440
DI 10.1371/journal.pntd.0004440
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DL1FC
UT WOS:000375376700007
PM 27074162
ER
PT J
AU Herman, SEM
Wiestner, A
AF Herman, Sarah E. M.
Wiestner, Adrian
TI Preclinical modeling of novel therapeutics in chronic lymphocytic
leukemia: the tools of the trade
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Chronic lymphocytic leukemia; Co-culture systems; Mouse models
ID B-CELL RECEPTOR; TYROSINE KINASE INHIBITOR; NURSE-LIKE CELLS; MARROW
STROMAL CELLS; BONE-MARROW; TUMOR PROLIFERATION; IN-VITRO; HEMATOLOGICAL
MALIGNANCIES; TARGETED THERAPIES; TRANSGENIC MOUSE
AB In the last decade our understanding of chronic lymphocytic leukemia (CLL) biology and pathogenesis has increased substantially. These insights have led to the development of several new agents with novel mechanisms of action prompting a change in therapeutic approaches from chemotherapy-based treatments to targeted therapies. Multiple preclinical models for drug development in CLL are available; however, with the advent of these targeted agents, it is becoming clear that not all models and surrogate readouts of efficacy are appropriate for all drugs. In this review we discuss in vitro and in vivo preclinical models, with a particular focus on the benefits and possible pitfalls of different model systems in the evaluation of novel therapeutics for the treatment of CLL. Published by Elsevier Inc.
C1 [Herman, Sarah E. M.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5256,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Herman, SEM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5256,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hermanse@mail.nih.gov
FU Intramural NIH HHS [Z01 HL002346-04, Z99 HL999999]
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U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD APR
PY 2016
VL 43
IS 2
BP 222
EP 232
DI 10.1053/j.seminoncol.2016.02.007
PG 11
WC Oncology
SC Oncology
GA DK8IP
UT WOS:000375170700005
PM 27040700
ER
PT J
AU Fourie, NH
Brown, JL
Jolly, CJ
Phillips-Conroy, JE
Rogers, J
Bernstein, RM
AF Fourie, Nicolaas H.
Brown, Janine L.
Jolly, Clifford J.
Phillips-Conroy, Jane E.
Rogers, Jeffrey
Bernstein, Robin M.
TI Sources of variation in hair cortisol in wild and captive non-human
primates
SO ZOOLOGY
LA English
DT Article
DE Cortisol; Hair cortisol analysis; Stress; Primates; Chronic stress
ID CHIMPANZEES PAN-TROGLODYTES; ARCHAEOLOGICAL HAIR; SALIVARY CORTISOL;
ANABOLIC-STEROIDS; BODY REGION; STRESS; BABOONS; AGE; CORTICOSTEROIDS;
POPULATIONS
AB Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. Published by Elsevier GmbH.
C1 [Fourie, Nicolaas H.; Bernstein, Robin M.] George Washington Univ, Ctr Adv Study Hominid Paleobiol, Dept Anthropol, 2110 G St NW, Washington, DC 20052 USA.
[Brown, Janine L.] Smithsonian Conservat Biol Inst, Ctr Species Survival, Front Royal, VA 22630 USA.
[Jolly, Clifford J.] NYU, Dept Anthropol, Rufus D Smith Hall,25 Waverly Pl, New York, NY 10003 USA.
[Phillips-Conroy, Jane E.] Washington Univ, Sch Med, Dept Anat & Neurobiol, 660 South Euclid Ave, St Louis, MO 63110 USA.
[Phillips-Conroy, Jane E.] Washington Univ, Dept Anthropol, McMillan Hall,Room 112,One Brookings Dr, St Louis, MO 63130 USA.
[Rogers, Jeffrey] Baylor Coll Med, Human Genome Sequencing Ctr, 1 Baylor Plaza, Houston, TX 77030 USA.
[Rogers, Jeffrey] Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA.
[Bernstein, Robin M.] Univ Colorado, Dept Anthropol, 1350 Pleasant St, Boulder, CO 80309 USA.
RP Fourie, NH (reprint author), NIH, Biobehav Branch, Div Intramural Res, Bethesda, MD 20892 USA.
EM fourienh@mail.nih.gov
OI Fourie, Nicolaas/0000-0002-5167-8570
FU San Diego Zoo; Center for the Advanced Study of Hominid Paleobiology at
the George Washington University; Lewis Cotlow Grant
FX We would like to thank Jean-Yves Robert and Dr. Benoit Quintard from the
Museum de Besancon for arranging for the collection of Papio papio
samples. We would like to thank Dr. Antoinette Kotze, Dr. Adrian Tordif
and Mark Howitt from the National Zoological Gardens in South Africa for
providing wild Papio ursinus samples from their collections and
projects, and the Tanzanian National Parks Authority (TANAPA) for
providing permission to conduct research in Mikumi National Park. We
would like to thank the San Diego Zoo for its support in this research.
We would also like to thank Dr. Rui Diogo for allowing the collection of
hair samples in the course of his research. We would also like to thank
Sarah Putman from the Smithsonian's Conservation Research Center for her
support and advice. We would like to thank Michael Holland for his
assistance in the laboratory. The research was supported with funds
provided by the Center for the Advanced Study of Hominid Paleobiology at
the George Washington University and through a Lewis Cotlow Grant. The
opinions expressed herein and the interpretation and reporting of these
data are the responsibility of the authors and in no way should be seen
as an official recommendation, interpretation, or policy of the National
Institutes of Health or the United States Government. The research
presented in this paper was conducted as part of Dr. Fourie's doctoral
research at the George Washington University before joining the NINR.
NR 57
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U1 10
U2 12
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0944-2006
J9 ZOOLOGY
JI Zoology
PD APR
PY 2016
VL 119
IS 2
BP 119
EP 125
DI 10.1016/j.zool.2016.01.001
PG 7
WC Zoology
SC Zoology
GA DJ7AQ
UT WOS:000374364700005
PM 26884274
ER
PT J
AU Hall, MD
Simeonov, A
Davis, MI
AF Hall, Matthew D.
Simeonov, Anton
Davis, Mindy I.
TI Avoiding Fluorescence Assay InterferenceThe Case for Diaphorase
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID SMALL-MOLECULE INHIBITORS; CHEMICAL LIBRARIES; RHODAMINE DIMERS; POTENT;
DISCOVERY; IDH1
AB Fluorescence is utilized as the output for a range of assay formats used in high-throughput screening (HTS). Interference with these assays from the compounds in libraries utilized in HTS is a well-recognized phenomenon, particularly for assays relying on UV excitation such as for direct detection of the oxidoreductase cofactors NADH or NADPH. In this study, we discuss these interference challenges and highlight the specific case of the diaphorase/resazurin system that can be coupled to enzymes utilizing NADH or NADPH. We review the utilization of this assay system in the literature and argue that the diaphorase/resazurin system is underutilized in assay development. It is the authors' hope that this Perspective and the accompanying Technical Brief in this issue will stimulate interest in a robust and sensitive coupling system to avoid assay fluorescence interference.
C1 [Hall, Matthew D.; Simeonov, Anton; Davis, Mindy I.] NIH, NCATS Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Davis, MI (reprint author), NIH, NCATS Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM davismi2@mail.nih.gov
FU NCATS Intramural Research Program of the National Institutes of Health
FX The authors thank Kyle Brimacombe for designing Figure 2. This work was
supported by the NCATS Intramural Research Program of the National
Institutes of Health. The content of this publication does not
necessarily reflect the views of policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 31
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U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
EI 1557-8127
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD APR
PY 2016
VL 14
IS 3
SI SI
BP 175
EP 179
DI 10.1089/adt.2016.707
PG 5
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA DK0ZM
UT WOS:000374641700004
PM 27078679
ER
PT J
AU Davis, MI
Shen, M
Simeonov, A
Hall, MD
AF Davis, Mindy I.
Shen, Min
Simeonov, Anton
Hall, Matthew D.
TI Diaphorase Coupling Protocols for Red-Shifting Dehydrogenase Assays
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID CHEMICAL LIBRARIES; IDH1
AB Dehydrogenases are an important target for the development of cancer therapeutics. Dehydrogenases either produce or consume NAD(P)H, which is fluorescent but at a wavelength where many compounds found in chemical libraries are also fluorescent. By coupling dehydrogenases to diaphorase, which utilizes NAD(P)H to produce the fluorescent molecule resorufin from resazurin, the assay can be red-shifted into a spectral region that reduces interference from compound libraries. Dehydrogenases that produce NAD(P)H, such as isocitrate dehydrogenase 1 (IDH1), can be read in kinetic mode. Dehydrogenases that consume NAD(P)H, such as mutant IDH1 R132H, can be read in endpoint mode. Here, we report protocols for robust and miniaturized 1,536-well assays for WT IDH1 and IDH1 R132H coupled to diaphorase, and the counterassays used to further detect compound interference with the coupling reagents. This coupling technique is applicable to dehydrogenases that either produce or consume NAD(P)H, and the examples provided here can act as guidelines for the development of high-throughput screens against this enzyme class.
C1 [Davis, Mindy I.; Shen, Min; Simeonov, Anton; Hall, Matthew D.] NIH, NCATS Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Hall, MD (reprint author), NIH, NCATS Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM hallma@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; Intramural Research Program of the
National Center for Advancing Translational Sciences, National
Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research and the
Intramural Research Program of the National Center for Advancing
Translational Sciences, National Institutes of Health. The content of
this publication does not necessarily reflect the views of policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 16
TC 2
Z9 2
U1 2
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
EI 1557-8127
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD APR
PY 2016
VL 14
IS 3
SI SI
BP 207
EP 212
DI 10.1089/adt.2016.706
PG 6
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA DK0ZM
UT WOS:000374641700007
PM 27078681
ER
PT J
AU Kim, C
Lee, H
Kang, H
Shin, JJ
Tak, H
Kim, W
Gorospe, M
Lee, EK
AF Kim, Chongtae
Lee, Heejin
Kang, Hoin
Shin, Jung Jae
Tak, Hyosun
Kim, Wook
Gorospe, Myriam
Lee, Eun Kyung
TI RNA-binding protein HuD reduces triglyceride production in pancreatic
beta cells by enhancing the expression of insulin-induced gene 1
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE RNA-binding protein; HuD; Triglyceride; INSIG1; SREBP1c
ID STEROL REGULATORY ELEMENT; FATTY-ACIDS; PROTEASOMAL DEGRADATION;
CHOLESTEROL HOMEOSTASIS; NEURITE OUTGROWTH; MESSENGER-RNAS; PC12 CELLS;
SREBP-1C; INSIG-1; PATHWAY
AB Although triglyceride (TG) accumulation in the pancreas leads to beta-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic beta cells have not been fully elucidated. Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic beta cells. Mouse insulinoma beta TC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (beta TC6-shHuD) contained higher TG levels compared to control cells. Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1 (SREBP1c), a key transcription factor for lipid production. We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses. By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels. We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice. Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic beta cells. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Kim, Chongtae; Lee, Heejin; Kang, Hoin; Tak, Hyosun; Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Dept Biochem, 222 Banpodaero, Seoul 137701, South Korea.
[Shin, Jung Jae; Kim, Wook] Ajou Univ, Dept Mol Sci & Technol, Suwon 443749, South Korea.
[Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Inst Aging & Metab Dis, Seoul 137701, South Korea.
RP Lee, EK (reprint author), Catholic Univ Korea, Coll Med, Dept Biochem, 222 Banpodaero, Seoul 137701, South Korea.
EM leeek@catholic.ac.kr
OI Lee, Eun Kyung/0000-0003-4207-2080
FU National Research Foundation of Korea (NRF) - Korea government
[2014R1A2A1A11053431, 2012R1A5A2047939, 2012M3A9D1054517, 2009-0093826];
NIA-IRP, NIH
FX We appreciate Jun Gi Rho for the technical assistance. We also thank
Professors Wado Akamatsu and Hideyuki Okano for providing pancreases of
HuD null mice. This work is supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea government
(2014R1A2A1A11053431, 2012R1A5A2047939 and 2012M3A9D1054517 for EKL and
2009-0093826 for WK). MG is supported by the NIA-IRP, NIH.
NR 62
TC 3
Z9 3
U1 3
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD APR
PY 2016
VL 1859
IS 4
BP 675
EP 685
DI 10.1016/j.bbagrm.2016.02.017
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DJ7CW
UT WOS:000374370500013
PM 26945853
ER
PT J
AU Greenlee, H
Molmenti, CLS
Falci, L
Ulmer, R
Deming-Halverson, S
DeRoo, LA
Sandler, DP
AF Greenlee, Heather
Molmenti, Christine L. Sardo
Falci, Laura
Ulmer, Ross
Deming-Halverson, Sandra
DeRoo, Lisa A.
Sandler, Dale P.
TI High use of complementary and alternative medicine among a large cohort
of women with a family history of breast cancer: the Sister Study
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Complementary and alternative medicine; Breast cancer; Breast cancer
risk; Gail model
ID LIFE-STYLE BEHAVIORS; NATIONAL-SURVEY; OVARIAN-CANCER; HIGH-RISK; WHITE;
INFORMATION; CHOICES; CAM
AB Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had a parts per thousand yen1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed.
C1 [Greenlee, Heather; Molmenti, Christine L. Sardo; Falci, Laura] Columbia Univ, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA.
[Greenlee, Heather; Molmenti, Christine L. Sardo] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Ulmer, Ross] WESTAT Corp, Durham, NC USA.
[Deming-Halverson, Sandra] Social & Sci Syst Inc, Durham, NC USA.
[Deming-Halverson, Sandra] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA.
[DeRoo, Lisa A.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, Durham, NC USA.
[DeRoo, Lisa A.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
RP Greenlee, H (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA.; Greenlee, H (reprint author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
EM hg2120@columbia.edu
OI Sandler, Dale/0000-0002-6776-0018
FU National Cancer Institute at the National Institutes of Health
[K23CA141052, T32CA009529-25]; Intramural Research Program of the NIH,
National Institute of Environmental Health Science [Z1A ES044005]
FX Funding was provided by the National Cancer Institute at the National
Institutes of Health (Grants K23CA141052 to H.G. and T32CA009529-25 to
C.S.M.) and the Intramural Research Program of the NIH, National
Institute of Environmental Health Science (Z1A ES044005).
NR 32
TC 0
Z9 0
U1 8
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD APR
PY 2016
VL 156
IS 3
BP 527
EP 538
DI 10.1007/s10549-016-3740-0
PG 12
WC Oncology
SC Oncology
GA DK1IU
UT WOS:000374666500014
PM 27017506
ER
PT J
AU Yang, SX
Polley, E
Lipkowitz, S
AF Yang, Sherry X.
Polley, Eric
Lipkowitz, Stanley
TI New insights on PI3K/AKT pathway alterations and clinical outcomes in
breast cancer
SO CANCER TREATMENT REVIEWS
LA English
DT Review
DE Breast cancer; Chemotherapy; HER2; Paclitaxel; pAKT; PIK3CA mutations
ID FACTOR RECEPTOR 2; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; PATHOLOGICAL
COMPLETE RESPONSE; PIK3CA MUTATIONS; ESTROGEN-RECEPTOR; ADJUVANT
CHEMOTHERAPY; PTEN LOSS; PHOSPHORYLATED AKT; PHASE-III; TRASTUZUMAB
RESISTANCE
AB PI3K/AKT signaling pathway plays an important role in tumorigenesis and regulates critical cellular functions including survival, proliferation and metabolism. PIK3CA mutations and AKT activation by phosphorylation (pAKT) are often detected in many cancers and especially at high frequencies in breast cancer. Mounting data suggest that PIK3CA mutations or pAKT are mostly associated with better or insignificant outcomes in estrogen receptor-positive (ER+) early stage breast cancer and tend to be with worse prognosis in ER disease. pAKT expression has been identified to predict paclitaxel chemotherapy benefit in node-positive breast cancer. Preclinical and neoadjuvant trial data suggest that PIK3CA alterations confer resistance to HER2-targeted therapy and are associated with lower pathological complete response (pCR) rate in HER2-positive breast cancer. However, recent results from randomized clinical trials of adjuvant and metastatic settings show that patients with mutant and wildtype PIK3CA tumors derived similar benefit from anti-HER2 therapy. This article, with our new insights, aims to decipher the mixed data and discusses the influence of the potential confounding factors in the assessments. We also share our views for validation of PI3K/AKT alterations in relation to clinical outcome in the context of specific breast cancer subtypes and treatment modalities towards further advance of the precision medicine for breast cancer treatment. Published by Elsevier Ltd.
C1 [Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Polley, Eric] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Lipkowitz, Stanley] NCI, Womens Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Polley, Eric] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA.
RP Yang, SX (reprint author), Bldg 37-Rm 1048,37 Convent Dr, Bethesda, MD 20892 USA.
EM Sherry.Yang@nih.gov
FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research
of the National cancer Institute, National Institutes of Health, USA
FX Supported in part by the Division of Cancer Treatment and Diagnosis and
the Center for Cancer Research of the National cancer Institute,
National Institutes of Health, USA.
NR 104
TC 18
Z9 19
U1 4
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0305-7372
EI 1532-1967
J9 CANCER TREAT REV
JI Cancer Treat. Rev.
PD APR
PY 2016
VL 45
BP 87
EP 96
DI 10.1016/j.ctrv.2016.03.004
PG 10
WC Oncology
SC Oncology
GA DK0OG
UT WOS:000374611500011
PM 26995633
ER
PT J
AU White, AJ
Bradshaw, PT
Herring, AH
Teitelbaum, SL
Beyea, J
Stellman, SD
Steck, SE
Mordukhovich, I
Eng, SM
Engel, LS
Conway, K
Hatch, M
Neugut, AI
Santella, RM
Gammon, MD
AF White, Alexandra J.
Bradshaw, Patrick T.
Herring, Amy H.
Teitelbaum, Susan L.
Beyea, Jan
Stellman, Steven D.
Steck, Susan E.
Mordukhovich, Irina
Eng, Sybil M.
Engel, Lawrence S.
Conway, Kathleen
Hatch, Maureen
Neugut, Alfred I.
Santella, Regina M.
Gammon, Marilie D.
TI Exposure to multiple sources of polycyclic aromatic hydrocarbons and
breast cancer incidence
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE Breast cancer; Polycyclic aromatic hydrocarbons; Smoking; Environmental
tobacco smoke; Grilled meat; Indoor air; Outdoor air
ID INDOOR AIR-POLLUTION; DIOXIN EXPOSURE; TOBACCO-SMOKE; MISSING-DATA; RED
MEAT; RISK; ASSOCIATION; PROJECT; COHORT; WOMEN
AB Background: Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction. Objectives: This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures.
Methods: In a population-based case-control study conducted on Long Island, New York (N =1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake.
Results: Most women were exposed to PAHs from multiple sources, and the most commonincluded active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR =1.20, 95%CrI = 1.03,1.40) and synthetic firelog burning (OR = 1.29, 95%CrI = 1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR = 1.45, 95%CrI = 1.02, 2.04).
Conclusions: Groups of PAH sources, particularly indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [White, Alexandra J.; Mordukhovich, Irina; Engel, Lawrence S.; Conway, Kathleen; Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, CB 7435,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
[Bradshaw, Patrick T.] Univ N Carolina, Dept Nutr, CB 7435,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, CB 7435,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
[Teitelbaum, Susan L.] Ichan Sch Med Mt Sinai, Dept Prevent Med, New York, NY USA.
[Beyea, Jan] Consulting Publ Interest CIPI, Lambertville, NJ USA.
[Stellman, Steven D.; Eng, Sybil M.; Neugut, Alfred I.] Columbia Univ, Dept Epidemiol, New York, NY 10027 USA.
[Neugut, Alfred I.] Columbia Univ, Dept Med, New York, NY 10027 USA.
[Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, New York, NY 10027 USA.
[Steck, Susan E.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Hatch, Maureen] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
RP White, AJ (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
EM whitea@unc.edu
OI Beyea, Jan/0000-0002-0547-880X; Engel, Lawrence/0000-0001-9268-4830
FU National Institute of Health [CA/ES66572, ES07018, ES10126, ES019459,
CA094061, CA57726]
FX Supported in part by National Institute of Health grants: CA/ES66572,
ES07018, ES10126, ES019459, CA094061 and CA57726.
NR 62
TC 7
Z9 7
U1 2
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD APR-MAY
PY 2016
VL 89-90
BP 185
EP 192
DI 10.1016/j.envint.2016.02.009
PG 8
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DK0LI
UT WOS:000374603900021
PM 26878284
ER
PT J
AU Christiansen, K
Dillingham, CM
Wright, NF
Saunders, RC
Vann, SD
Aggleton, JP
AF Christiansen, Kat
Dillingham, Christopher M.
Wright, Nicholas F.
Saunders, Richard C.
Vann, Seralynne D.
Aggleton, John P.
TI Complementary subicular pathways to the anterior thalamic nuclei and
mammillary bodies in the rat and macaque monkey brain
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE anatomy; fornix; hippocampus; memory; subiculum
ID MAMILLARY-BODY LESIONS; HIPPOCAMPAL-FORMATION; ENTORHINAL CORTEX;
RHESUS-MONKEY; HORSERADISH-PEROXIDASE; TEMPORAL-LOBE; LAMINAR
ORGANIZATION; MACACA-FASCICULARIS; CEREBRAL-CORTEX; TOPOGRAPHIC
ORGANIZATION
AB The origins of the hippocampal (subicular) projections to the anterior thalamic nuclei and mammillary bodies were compared in rats and macaque monkeys using retrograde tracers. These projections form core components of the Papez circuit, which is vital for normal memory. The study revealed a complex pattern of subicular efferents, consistent with the presence of different, parallel information streams, whose segregation appears more marked in the rat brain. In both species, the cells projecting to the mammillary bodies and anterior thalamic nuclei showed laminar separation but also differed along other hippocampal axes. In the rat, these diencephalic inputs showed complementary topographies in the proximal-distal (columnar) plane, consistent with differential involvement in object-based (proximal subiculum) and context-based (distal subiculum) information. The medial mammillary inputs, which arose along the anterior-posterior extent of the rat subiculum, favoured the central subiculum (septal hippocampus) and the more proximal subiculum (temporal hippocampus). In contrast, anterior thalamic inputs were largely confined to the dorsal (i.e. septal and intermediate) subiculum, where projections to the anteromedial nucleus favoured the proximal subiculum while those to the anteroventral nucleus predominantly arose in the distal subiculum. In the macaque, the corresponding diencephalic inputs were again distinguished by anterior-posterior topographies, as subicular inputs to the medial mammillary bodies predominantly arose from the posterior hippocampus while subicular inputs to the anteromedial thalamic nucleus predominantly arose from the anterior hippocampus. Unlike the rat, there was no clear evidence of proximal-distal separation as all of these medial diencephalic projections preferentially arose from the more distal subiculum.
C1 [Christiansen, Kat; Dillingham, Christopher M.; Wright, Nicholas F.; Vann, Seralynne D.; Aggleton, John P.] Cardiff Univ, Sch Psychol, Tower Bldg 70,Pk Pl, Cardiff CF10 3AT, S Glam, Wales.
[Saunders, Richard C.] NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA.
RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Tower Bldg 70,Pk Pl, Cardiff CF10 3AT, S Glam, Wales.
EM aggleton@cf.ac.uk
OI Aggleton, John/0000-0002-5573-1308
FU Wellcome Trust [WT103722/Z/14/Z, WT090954AIA]
FX This work was supported by the Wellcome Trust (grant numbers
WT103722/Z/14/Z and WT090954AIA).
NR 136
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD APR
PY 2016
VL 43
IS 8
BP 1044
EP 1061
DI 10.1111/ejn.13208
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA DK1BA
UT WOS:000374645700006
PM 26855336
ER
PT J
AU Panyakaew, P
Cho, HJ
Srivanitchapoom, P
Popa, T
Wu, TX
Hallett, M
AF Panyakaew, Pattamon
Cho, Hyun Joo
Srivanitchapoom, Prachaya
Popa, Traian
Wu, Tianxia
Hallett, Mark
TI Cerebellar brain inhibition in the target and surround muscles during
voluntary tonic activation
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cerebellar brain inhibition (CBI); cerebellum; surround muscles; TMS;
tonic activation
ID TRANSCRANIAL MAGNETIC STIMULATION; FOCAL HAND DYSTONIA; HUMAN MOTOR
SYSTEM; BASAL GANGLIA; CORTEX; MOVEMENT; HUMANS; ROLES
AB Motor surround inhibition is the neural mechanism that selectively favours the contraction of target muscles and inhibits nearby muscles to prevent unwanted movements. This inhibition was previously reported at the onset of a movement, but not during a tonic contraction. Cerebellar brain inhibition (CBI) is reduced in active muscles during tonic activation; however, it has not been studied in the surround muscles. CBI was evaluated in the first dorsal interosseus (FDI) muscle as the target muscle, and the abductor digiti minimi, flexor carpi radialis and extensor carpi radialis muscles as surround muscles, during rest and tonic activation of the FDI muscle in 21 subjects. Cerebellar stimulation was performed under magnetic resonance imaging-guided neuronavigation targeting lobule VIII of the cerebellar hemisphere. Stimulus intensities for cerebellar stimulation were based on the resting motor cortex threshold (RMT) and adjusted for the depth difference between the cerebellar and motor cortices. We used 90-120% of the adjusted RMT as the conditioning stimulus intensity during rest. The intensity that generated the best CBI at rest in the FDI muscle was selected for use during tonic activation. During selective tonic activation of the FDI muscle, CBI was significantly reduced only for the FDI muscle, and not for the surround muscles. Unconditioned motor evoked potential sizes were increased in all muscles during FDI muscle tonic activation as compared with rest, despite background electromyography activity increasing only for the FDI muscle. Our study suggests that the cerebellum may play an important role in selective tonic finger movement by reducing its inhibition in the motor cortex only for the relevant agonist muscle.
C1 [Panyakaew, Pattamon; Cho, Hyun Joo; Srivanitchapoom, Prachaya; Popa, Traian; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Panyakaew, Pattamon] Chulalongkorn Univ, Fac Med, Dept Med, Chulalongkorn Ctr Excellence Parkinson Dis & Rela, Bangkok, Thailand.
[Panyakaew, Pattamon] King Chulalongkorn Mem Hosp, Thai Red Cross Soc, Bangkok, Thailand.
[Srivanitchapoom, Prachaya] Mahidol Univ, Siriraj Hosp, Fac Med, Div Neurol,Dept Med, Bangkok 10700, Thailand.
[Wu, Tianxia] NINDS, Clin Neurosci Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), 10 Ctr Dr MSC 1428,Bldg 10,Room 7D37, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
RI Popa, Traian/B-7691-2016
OI Popa, Traian/0000-0003-1160-4830
FU NINDS, NIH Intramural Program
FX This research was supported by the NINDS, NIH Intramural Program.
NR 32
TC 0
Z9 0
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD APR
PY 2016
VL 43
IS 8
BP 1075
EP 1081
DI 10.1111/ejn.13211
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DK1BA
UT WOS:000374645700008
PM 26900871
ER
PT J
AU Chen, YW
Sagar, V
Len, HS
Peterson, K
Fan, JG
Mishra, S
McMurtry, J
Wilmarth, PA
David, LL
Wistow, G
AF Chen, Yingwei
Sagar, Vatsala
Len, Hoay-Shuen
Peterson, Katherine
Fan, Jianguo
Mishra, Sanghamitra
McMurtry, John
Wilmarth, Phillip A.
David, Larry L.
Wistow, Graeme
TI gamma-Crystallins of the chicken lens: remnants of an ancient vertebrate
gene family in birds
SO FEBS JOURNAL
LA English
DT Article
DE crystallin; evolution; eye; promoter; protein folding; proteomics
ID SEQUENCE TAG ANALYSIS; S-CRYSTALLIN; EYE LENS; NEIBANK PROJECT; SEARCH
TOOL; EXPRESSION; PROTEIN; EVOLUTION; RECRUITMENT; ENZYME
AB gamma-Crystallins, abundant proteins of vertebrate lenses, were thought to be absent from birds. However, bird genomes contain well-conserved genes for S- and N-crystallins. Although expressed sequence tag analysis of chicken eye found no transcripts for these genes, RT-PCR detected spliced transcripts for both genes in chicken lens, with lower levels in cornea and retina/retinal pigment epithelium. The level of mRNA for S in chicken lens was relatively very low even though the chicken crygs gene promoter had lens-preferred activity similar to that of mouse. Chicken S was detected by a peptide antibody in lens, but not in other ocular tissues. Low levels of S and N proteins were detected in chicken lens by shotgun mass spectroscopy. Water-soluble and water-insoluble lens fractions were analyzed and 1934 proteins (< 1% false discovery rate) were detected, increasing the known chicken lens proteome 30-fold. Although chicken S is well conserved in protein sequence, it has one notable difference in leucine 16, replacing a surface glutamine conserved in other -crystallins, possibly affecting solubility. However, L16 and engineered Q16 versions were both highly soluble and had indistinguishable circular dichroism, tryptophan fluorescence and heat stability (melting temperature T-m similar to 65 degrees C) profiles. L16 has been present in birds for over 100 million years and may have been adopted for a specific protein interaction in the bird lens. However, evolution has clearly reduced or eliminated expression of ancestral -crystallins in bird lenses. The conservation of genes for S- and N-crystallins suggests they may have been preserved for reasons unrelated to the bulk properties of the lens.
C1 [Chen, Yingwei; Sagar, Vatsala; Len, Hoay-Shuen; Peterson, Katherine; Fan, Jianguo; Mishra, Sanghamitra; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bg 6,Rm 106, Bethesda, MD 20892 USA.
[McMurtry, John] ARS, USDA, Southern Plains Area, East Coll Stn, Dallas, TX USA.
[Wilmarth, Phillip A.; David, Larry L.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Sch Med, Portland, OR 97201 USA.
RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct Genom, NIH, Bg 6,Rm 106, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
FU NEI Intramural Program; NIH [EY010572, EY007755]
FX This work was performed with the support of the NEI Intramural Program
and NIH grants EY010572 and EY007755. Some experiments were performed at
the NHLBI Biophysics Core.
NR 58
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD APR
PY 2016
VL 283
IS 8
BP 1516
EP 1530
DI 10.1111/febs.13689
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK1NV
UT WOS:000374680500012
PM 26913478
ER
PT J
AU Barker, DJ
Root, DH
Zhang, SL
Morales, M
AF Barker, David J.
Root, David H.
Zhang, Shiliang
Morales, Marisela
TI Multiplexed neurochemical signaling by neurons of the ventral tegmental
area
SO JOURNAL OF CHEMICAL NEUROANATOMY
LA English
DT Review
DE Reward; Addiction; Depression; Aversion; Co-transmission; Dopamine;
Glutamate; GABA
ID VESICULAR GLUTAMATE TRANSPORTER; MIDBRAIN DOPAMINE NEURONS; MEDIOLATERAL
FUNCTIONAL DICHOTOMY; NUCLEUS-ACCUMBENS DOPAMINE; SUBSTANTIA-NIGRA
COMPACTA; GABA-CONTAINING NEURONS; PHASIC FIRING PATTERNS; LATERAL
HABENULA; GABAERGIC PHENOTYPE; AVERSIVE STIMULI
AB The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in 'multiplexed' neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression. Published by Elsevier B.V.
C1 [Barker, David J.; Root, David H.; Zhang, Shiliang; Morales, Marisela] NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, 251 Bayview Blvd Suite 200, Baltimore, MD 21224 USA.
RP Morales, M (reprint author), NIDA, Neuronal Networks Sect, Integrat Neurosci Res Branch, 251 Bayview Blvd Suite 200, Baltimore, MD 21224 USA.
EM mmorales@intra.nida.nih.gov
OI Root, David/0000-0002-1927-2175
FU Intramural Research Program of the National Institute on Drug Abuse, US
National Institutes of Health (IRP/NIDA/NIH)
FX The Intramural Research Program of the National Institute on Drug Abuse,
US National Institutes of Health (IRP/NIDA/NIH) supported this work.
NR 170
TC 5
Z9 5
U1 5
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0891-0618
EI 1873-6300
J9 J CHEM NEUROANAT
JI J. Chem. Neuroanat.
PD APR
PY 2016
VL 73
SI SI
BP 33
EP 42
DI 10.1016/j.jchemneu.2015.12.016
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DK0ST
UT WOS:000374623200005
PM 26763116
ER
PT J
AU Piccart-Gebhart, M
Holmes, E
Baselga, J
de Azambuja, E
Dueck, AC
Viale, G
Zujewski, JA
Goldhirsch, A
Armour, A
Pritchard, KI
McCullough, AE
Dolci, S
McFadden, E
Holmes, AP
Liu, TH
Eidtmann, H
Dinh, P
Di Cosimo, S
Harbeck, N
Tjulandin, S
Im, YH
Huang, CS
Dieras, V
Hillman, DW
Wolff, AC
Jackisch, C
Lang, I
Untch, M
Smith, I
Boyle, F
Xu, BH
Gomez, H
Suter, T
Gelber, RD
Perez, EA
AF Piccart-Gebhart, Martine
Holmes, Eileen
Baselga, Jose
de Azambuja, Evandro
Dueck, Amylou C.
Viale, Giuseppe
Zujewski, Jo Anne
Goldhirsch, Aron
Armour, Alison
Pritchard, Kathleen I.
McCullough, Ann E.
Dolci, Stella
McFadden, Eleanor
Holmes, Andrew P.
Liu Tonghua
Eidtmann, Holger
Phuong Dinh
Di Cosimo, Serena
Harbeck, Nadia
Tjulandin, Sergei
Im, Young-Hyuck
Huang, Chiun-Sheng
Dieras, Veronique
Hillman, David W.
Wolff, Antonio C.
Jackisch, Christian
Lang, Istvan
Untch, Michael
Smith, Ian
Boyle, Frances
Xu, Binghe
Gomez, Henry
Suter, Thomas
Gelber, Richard D.
Perez, Edith A.
TI Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth
Factor Receptor 2-Positive Breast Cancer: Results From the Randomized
Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization
Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID OPEN-LABEL; PLUS CAPECITABINE; CHEMOTHERAPY; THERAPY; SURVIVAL;
EFFICACY; SAFETY; COMBINATION; INHIBITOR; DOCETAXEL
AB Background
Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain.
Methods
In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T. L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T.
Results
Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P <= .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T. L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms.
Conclusion
Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.
C1 [de Azambuja, Evandro] Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium.
[Piccart-Gebhart, Martine] Univ Libre Bruxelles, Brussels, Belgium.
[Holmes, Eileen; McFadden, Eleanor; Holmes, Andrew P.] Frontier Sci Scotland, Kincraig, Kingussie, Scotland.
[Baselga, Jose] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[de Azambuja, Evandro; Dolci, Stella] Breast European Adjuvant Study Team, Brussels, Belgium.
[Dueck, Amylou C.; McCullough, Ann E.] Mayo Clin, Scottsdale, AZ USA.
[Viale, Giuseppe] Univ Milan, Milan, Italy.
[Viale, Giuseppe; Goldhirsch, Aron] Ist Europeo Oncol, Milan, Italy.
[Zujewski, Jo Anne] NCI, Bethesda, MD 20892 USA.
[Goldhirsch, Aron] Osped Reg Lugano, Viganello Lugano, Switzerland.
[Armour, Alison] GlaxoSmithKline, Collegeville, PA USA.
[Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada.
[Liu Tonghua] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Liu Tonghua; Xu, Binghe] China Acad Chinese Med Sci, Beijing, Peoples R China.
[Eidtmann, Holger] Univ Hosp Kiel, Kiel, Germany.
[Phuong Dinh] Breast Int Grp, Brussels, Belgium.
[Di Cosimo, Serena] Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy.
[Di Cosimo, Serena] SOLTI Breast Canc Res Grp, Barcelona, Spain.
[Harbeck, Nadia] Frauenklin Univ Munchen, Munich, Germany.
[Tjulandin, Sergei] RAMS, Blokhin Russian Canc Res Ctr, Moscow, Russia.
[Im, Young-Hyuck] Korean Canc Study Grp, Seoul, South Korea.
[Im, Young-Hyuck] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea.
[Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Taipei, Taiwan.
[Dieras, Veronique] Inst Curie, Paris, France.
[Hillman, David W.] Mayo Clin, Rochester, MN USA.
[Wolff, Antonio C.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Jackisch, Christian] Klinikum Offenbach, Offenbach, Germany.
[Lang, Istvan] Natl Inst Oncol, Budapest, Hungary.
[Untch, Michael] Helios Klinikum Berlin Buch, Berlin, Germany.
[Smith, Ian] Royal Marsden Hosp NHS Trust Surrey, Sutton, Surrey, England.
[Boyle, Frances] Univ Sydney, Mater Hosp, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW, Australia.
[Gomez, Henry] Inst Nacl Enfermedades Neoplas, Lima, Peru.
[Suter, Thomas] Univ Hosp Bern, CH-3010 Bern, Switzerland.
[Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
[Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA.
RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium.
EM martine.piccart@bordet.be
RI Serena, Di Cosimo/E-9418-2017
OI Serena, Di Cosimo/0000-0002-4666-8052
FU GlaxoSmithKline; National Cancer Institute of the National Institutes of
Health [U10CA180821, U10CA180882, CA025224]
FX Supported by GlaxoSmithKline and the National Cancer Institute of the
National Institutes of Health under Grant No. U10CA180821 and
U10CA180882 to the Alliance for Clinical Trials in Oncology and CA025224
to the legacy North Central Cancer Treatment Group.
NR 33
TC 29
Z9 29
U1 0
U2 10
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 1
PY 2016
VL 34
IS 10
BP 1034
EP +
DI 10.1200/JCO.2015.62.1797
PG 25
WC Oncology
SC Oncology
GA DJ6PA
UT WOS:000374334200008
PM 26598744
ER
PT J
AU Brudno, JN
Somerville, RPT
Shi, V
Rose, JJ
Halverson, DC
Fowler, DH
Gea-Banacloche, JC
Pavletic, SZ
Hickstein, DD
Lu, TYL
Feldman, SA
Iwamoto, AT
Kurlander, R
Maric, I
Goy, A
Hansen, BG
Wilder, JS
Blacklock-Schuver, B
Hakim, FT
Rosenberg, SA
Gress, RE
Kochenderfer, JN
AF Brudno, Jennifer N.
Somerville, Robert P. T.
Shi, Victoria
Rose, Jeremy J.
Halverson, David C.
Fowler, Daniel H.
Gea-Banacloche, Juan C.
Pavletic, Steven Z.
Hickstein, Dennis D.
Lu, Tangying L.
Feldman, Steven A.
Iwamoto, Alexander T.
Kurlander, Roger
Maric, Irina
Goy, Andre
Hansen, Brenna G.
Wilder, Jennifer S.
Blacklock-Schuver, Bazetta
Hakim, Frances T.
Rosenberg, Steven A.
Gress, Ronald E.
Kochenderfer, James N.
TI Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor
Induce Remissions of B-Cell Malignancies That Progress After Allogeneic
Hematopoietic Stem-Cell Transplantation Without Causing
Graft-Versus-Host Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LEUKEMIA; LYMPHOMA; LYMPHOCYTES; DIAGNOSIS; RELAPSE; CANCER; CD19;
MANAGEMENT; RESPONSES; CRITERIA
AB Purpose
Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues.
Methods
We conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor.
Results
Eight of 20 treated patients obtained remission, which included six complete remissions (CRs) and two partial remissions. The response rate was highest for acute lymphoblastic leukemia, with four of five patients obtaining minimal residual disease-negative CR. Responses also occurred in chronic lymphocytic leukemia and lymphoma. The longest ongoing CR was more than 30 months in a patient with chronic lymphocytic leukemia. New-onset acute graft-versus-host disease after CAR T-cell infusion developed in none of the patients. Toxicities included fever, tachycardia, and hypotension. Peak blood CAR T-cell levels were higher in patients who obtained remissions than in those who did not. Programmed cell death protein-1 expression was significantly elevated on CAR T cells after infusion. Presence of blood B cells before CAR T-cell infusion was associated with higher postinfusion CAR T-cell levels.
Conclusion
Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT.
C1 [Brudno, Jennifer N.; Somerville, Robert P. T.; Shi, Victoria; Rose, Jeremy J.; Halverson, David C.; Fowler, Daniel H.; Gea-Banacloche, Juan C.; Pavletic, Steven Z.; Hickstein, Dennis D.; Lu, Tangying L.; Feldman, Steven A.; Iwamoto, Alexander T.; Hansen, Brenna G.; Blacklock-Schuver, Bazetta; Hakim, Frances T.; Rosenberg, Steven A.; Gress, Ronald E.; Kochenderfer, James N.] NCI, Bethesda, MD 20892 USA.
[Kurlander, Roger; Maric, Irina] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Wilder, Jennifer S.] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Goy, Andre] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
RP Kochenderfer, JN (reprint author), NCI, NIH, Bldg 10,Room 3-3330, Bethesda, MD 20892 USA.
EM kochendj@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute; National Cancer
Institute [HHSN261200800001E]
FX Supported by intramural funding of the Center for Cancer Research,
National Cancer Institute. This project has been funded in part with
federal funds from the National Cancer Institute, under contract
HHSN261200800001E.
NR 42
TC 43
Z9 46
U1 6
U2 14
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 1
PY 2016
VL 34
IS 10
BP 1112
EP +
DI 10.1200/JCO.2015.64.5929
PG 12
WC Oncology
SC Oncology
GA DJ6PA
UT WOS:000374334200018
PM 26811520
ER
PT J
AU Harris, LN
Ismaila, N
McShane, LM
Andre, F
Collyar, DE
Gonzalez-Angulo, AM
Hammond, EH
Kuderer, NM
Liu, MC
Mennel, RG
Van Poznak, C
Bast, RC
Hayes, DF
AF Harris, Lyndsay N.
Ismaila, Nofisat
McShane, Lisa M.
Andre, Fabrice
Collyar, Deborah E.
Gonzalez-Angulo, Ana M.
Hammond, Elizabeth H.
Kuderer, Nicole M.
Liu, Minetta C.
Mennel, Robert G.
Van Poznak, Catherine
Bast, Robert C.
Hayes, Daniel F.
TI Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for
Women With Early-Stage Invasive Breast Cancer: American Society of
Clinical Oncology Clinical Practice Guideline
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LATE-DISTANT RECURRENCE; 70-GENE PROGNOSIS-SIGNATURE;
TOPOISOMERASE-II-ALPHA; TUMOR-INFILTRATING LYMPHOCYTES;
ESTROGEN-RECEPTOR; RANDOMIZED-TRIALS; PREDICTIVE-VALUE; PAM50 RISK;
POSTMENOPAUSAL WOMEN; ENDOCRINE THERAPY
AB Purpose
To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer.
Methods
A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations.
Results
The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens.
Recommendations
In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.
C1 [Harris, Lyndsay N.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Ismaila, Nofisat] Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
[McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Andre, Fabrice] Inst Gustave Roussy, Paris, France.
[Collyar, Deborah E.] Patient Advocates Res, Mitrowski, CA USA.
[Hammond, Elizabeth H.] Univ Utah, Salt Lake City, UT USA.
[Hammond, Elizabeth H.] Intermt Hlth Care, Salt Lake City, UT USA.
[Gonzalez-Angulo, Ana M.; Bast, Robert C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mennel, Robert G.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Mennel, Robert G.] Texas Oncol PA, Dallas, TX USA.
[Kuderer, Nicole M.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Liu, Minetta C.] Mayo Clin, Coll Med, Rochester, MN USA.
[Van Poznak, Catherine; Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Harris, LN (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
RI Bast, Robert/E-6585-2011
OI Bast, Robert/0000-0003-4621-8462
FU NCI NIH HHS [P50 CA058223]
NR 83
TC 49
Z9 50
U1 11
U2 17
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 1
PY 2016
VL 34
IS 10
BP 1134
EP +
DI 10.1200/JCO.2015.65.2289
PG 19
WC Oncology
SC Oncology
GA DJ6PA
UT WOS:000374334200021
PM 26858339
ER
PT J
AU Qiang, GF
Kong, HW
Fang, DF
McCann, M
Yang, XY
Du, GH
Bluher, M
Zhu, JF
Liew, CW
AF Qiang, Guifen
Kong, Hyerim Whang
Fang, Difeng
McCann, Maximilian
Yang, Xiuying
Du, Guanhua
Bluher, Matthias
Zhu, Jinfang
Liew, Chong Wee
TI The obesity-induced transcriptional regulator TRIP-Br2 mediates visceral
fat endoplasmic reticulum stress-induced inflammation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ADIPOSE-TISSUE; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION; WAIST
CIRCUMFERENCE; MOUSE MODEL; BODY-FAT; EXPRESSION; DEPOTS; GATA;
THERMOGENESIS
AB The intimate link between location of fat accumulation and metabolic disease risk and depot-specific differences is well established, but how these differences between depots are regulated at the molecular level remains largely unclear. Here we show that TRIP-Br2 mediates endoplasmic reticulum (ER) stress-induced inflammatory responses in visceral fat. Using in vitro, ex vivo and in vivo approaches, we demonstrate that obesity-induced circulating factors upregulate TRIP-Br2 specifically in visceral fat via the ER stress pathway. We find that ablation of TRIP-Br2 ameliorates both chemical and physiological ER stress-induced inflammatory and acute phase response in adipocytes, leading to lower circulating levels of inflammatory cytokines. Using promoter assays, as well as molecular and pharmacological experiments, we show that the transcription factor GATA3 is responsible for the ER stress-induced TRIP-Br2 expression in visceral fat. Taken together, our study identifies molecular regulators of inflammatory response in visceral fat that-given that these pathways are conserved in humans-might serve as potential therapeutic targets in obesity.
C1 [Qiang, Guifen; Kong, Hyerim Whang; McCann, Maximilian; Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Coll Med, 835 S Wolcott Ave,M-C901,MSB E-202, Chicago, IL 60612 USA.
[Fang, Difeng; Zhu, Jinfang] NIAID, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Yang, Xiuying; Du, Guanhua] Chinese Acad Med Sci, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med, Beijing 100050, Peoples R China.
[Yang, Xiuying; Du, Guanhua] Peking Union Med Coll, Beijing 100050, Peoples R China.
[Bluher, Matthias] Univ Leipzig, Dept Med, Liebigstr 18, D-04103 Leipzig, Germany.
RP Liew, CW (reprint author), Univ Illinois, Dept Physiol & Biophys, Coll Med, 835 S Wolcott Ave,M-C901,MSB E-202, Chicago, IL 60612 USA.
EM cwliew@uic.edu
RI Zhu, Jinfang/B-7574-2012;
OI 杨, 秀颖/0000-0001-8500-3128
FU Research Open Access Publishing (ROAAP) Fund of the University of
Illinois at Chicago; Novo Nordisk Great Lakes Science Forum Award;
RayBiotech Innovative Research Grant Award; Center for Society for
Clinical and Translational Research Early Career Development Award; UIC
Startup fund; Deutsche Forschungsgemeinschaft [SFB 1052]; intramural
research program of NIAID, NIH; [K99 DK090210]; [R00 DK090210]
FX We thank J.L Kirkland MD PhD and Martin Wabitsch MD PhD for providing
human preadipocyte and SBGS cell lines. This publication is partly
supported by the Research Open Access Publishing (ROAAP) Fund of the
University of Illinois at Chicago. This work was supported by K99
DK090210, R00 DK090210, Novo Nordisk Great Lakes Science Forum Award,
RayBiotech Innovative Research Grant Award, Center for Society for
Clinical and Translational Research Early Career Development Award and
UIC Startup fund (C.W.L.). The human studies were supported by a grant
of the Deutsche Forschungsgemeinschaft, Obesity Mechanisms (SFB 1052,
B01 to M.B.). D. Fang and J. Zhu are supported by the intramural
research program of NIAID, NIH.
NR 43
TC 3
Z9 3
U1 4
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 11378
DI 10.1038/ncomms11378
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK1PB
UT WOS:000374684000001
PM 27109496
ER
PT J
AU Ewers, EC
Pratt, WD
Twenhafel, NA
Shamblin, J
Donnelly, G
Esham, H
Wlazlowski, C
Johnson, JC
Botto, M
Hensley, LE
Goff, AJ
AF Ewers, Evan C.
Pratt, William D.
Twenhafel, Nancy A.
Shamblin, Joshua
Donnelly, Ginger
Esham, Heather
Wlazlowski, Carly
Johnson, Joshua C.
Botto, Miriam
Hensley, Lisa E.
Goff, Arthur J.
TI Natural History of Aerosol Exposure with Marburg Virus in Rhesus
Macaques
SO VIRUSES-BASEL
LA English
DT Article
DE filovirus; nonhuman primate; Marburg virus; aerosol; telemetry; animal
model
ID EBOLA HEMORRHAGIC-FEVER; CYNOMOLGUS MACAQUES; INFECTED PATIENTS; ANGOLA
INFECTION; ZAIRE-EBOLAVIRUS; DISEASE; PATHOGENESIS; APOPTOSIS;
COAGULATION; RESPONSES
AB Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.
C1 [Ewers, Evan C.; Twenhafel, Nancy A.; Goff, Arthur J.] Tripler Army Med Ctr, Dept Med, Honolulu, HI 96859 USA.
[Pratt, William D.; Twenhafel, Nancy A.; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Botto, Miriam; Goff, Arthur J.] US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Johnson, Joshua C.; Hensley, Lisa E.] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
RP Pratt, WD (reprint author), US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
EM evan.c.ewers.mil@mail.mil; william.d.pratt4.ctr@mail.mil;
nancy.a.twenhafel.mil@mail.mil; joshua.d.shamblin1.civ@mail.mil;
ginger.c.donnelly.ctr@mail.mil; heather.l.esham.civ@mail.mil;
carly.b.wlazlowski.ctr@mail.mil; joshua.johnson@nih.gov;
miriam.a.botto.civ@mail.mil; lisa.hensley@nih.gov;
arthur.j.goff.civ@mail.mil
OI Johnson, Joshua/0000-0002-5677-3841; Ewers, Evan/0000-0002-1384-9973
FU Defense Threat Reduction Agency
FX Financial contributions for this work were provided by the Defense
Threat Reduction Agency. The authors acknowledge the contributions of
Shannan Hall-Ursone for implant and catheter surgery of the animals, and
David O'Brien and Wendy Giles for technical expertise with these
studies.
NR 40
TC 0
Z9 0
U1 2
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD APR
PY 2016
VL 8
IS 4
AR 87
DI 10.3390/v8040087
PG 16
WC Virology
SC Virology
GA DK8DQ
UT WOS:000375157800001
PM 27043611
ER
PT J
AU Carter, CA
Rajan, A
Keen, C
Szabo, E
Khozin, S
Thomas, A
Brzezniak, C
Guha, U
Doyle, LA
Steinberg, SM
Xi, L
Raffeld, M
Tomita, Y
Lee, MJ
Lee, S
Trepel, JB
Reckamp, KL
Koehler, S
Gitlitz, B
Salgia, R
Gandara, D
Vokes, E
Giaccone, G
AF Carter, C. A.
Rajan, A.
Keen, C.
Szabo, E.
Khozin, S.
Thomas, A.
Brzezniak, C.
Guha, U.
Doyle, L. A.
Steinberg, S. M.
Xi, L.
Raffeld, M.
Tomita, Y.
Lee, M. J.
Lee, S.
Trepel, J. B.
Reckamp, K. L.
Koehler, S.
Gitlitz, B.
Salgia, R.
Gandara, D.
Vokes, E.
Giaccone, G.
TI Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type
advanced nonsmall-cell lung cancer
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE nonsmall-cell lung cancer; MEK; EGFR; KRAS; selumetinib; erlotinib
ID MEK INHIBITION; AZD6244 ARRY-142886; OPEN-LABEL; PHASE-II; IN-VITRO;
MUTATIONS; THERAPY; RESISTANCE; TUMORS; TRIAL
AB This study failed to show improvement of combination therapy using an epidermal growth factor receptor tyrosine kinase inhibitor combined with an MEK inhibitor over single-agent therapy in KRAS wild-type and mutant patients. Toxicity was significantly increased when the two drugs are combined.KRAS mutations in NSCLC are associated with a lack of response to epidermal growth factor receptor inhibitors. Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway.
Advanced nonsmall-cell lung cancer (NSCLC) patients failing one to two prior regimens underwent KRAS profiling. KRAS wild-type patients were randomized to erlotinib (150 mg daily) or a combination of selumetinib (150 mg daily) with erlotinib (100 mg daily). KRAS mutant patients were randomized to selumetinib (75 mg b.i.d.) or the combination. The primary end points were progression-free survival (PFS) for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Biomarker studies of ERK phosphorylation and immune subsets were carried out.
From March 2010 to May 2013, 89 patients were screened; 41 KRAS mutant and 38 KRAS wild-type patients were enrolled. Median PFS in the KRAS wild-type arm was 2.4 months [95% confidence interval (CI) 1.3-3.7] for erlotinib alone and 2.1 months (95% CI 1.8-5.1) for the combination. The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. Combination therapy resulted in increased toxicities, requiring dose reductions (56%) and discontinuation (8%). Programmed cell death-1 expression on regulatory T cells (Tregs), Tim-3 on CD8+ T cells and Th17 levels were associated with PFS and overall survival in patients receiving selumetinib.
This study failed to show improvement in ORR or PFS with combination therapy of selumetinib and erlotinib over monotherapy in KRAS mutant and KRAS wild-type advanced NSCLC. The association of immune subsets and immune checkpoint receptor expression with selumetinib may warrant further studies.
C1 [Carter, C. A.; Brzezniak, C.] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA.
[Rajan, A.; Keen, C.; Khozin, S.; Thomas, A.; Guha, U.; Tomita, Y.; Lee, M. J.; Lee, S.; Trepel, J. B.; Giaccone, G.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Szabo, E.] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Doyle, L. A.] NIH, Canc Therapy Evaluat Program, Bldg 10, Bethesda, MD 20892 USA.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Xi, L.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Reckamp, K. L.; Koehler, S.] City Hope Comprehens Canc Ctr, Dept Hematol & Med Oncol, Duarte, CA USA.
[Gitlitz, B.] Univ So Calif, Dept Internal Med, Los Angeles, CA USA.
[Salgia, R.; Vokes, E.] Univ Chicago, Radiat & Cellular Oncol, Med & Biol Sci, Chicago, IL 60637 USA.
[Gandara, D.] Univ Calif Davis, Div Hematol & Oncol, Ctr Canc, Sacramento, CA 95817 USA.
[Giaccone, G.] Georgetown Univ, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd, Washington, DC 20007 USA.
RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd, Washington, DC 20007 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Reckamp,
Karen/0000-0002-9213-0325
FU National Cancer Institute, National Institutes of Health; CTEP grant
system: NO1 contract system [NCT: 01229150 CTEP: 8444]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health. NCT:
01229150 CTEP: 8444, supported by the CTEP grant system: NO1 contract
system.
NR 30
TC 9
Z9 9
U1 2
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD APR
PY 2016
VL 27
IS 4
BP 693
EP 699
DI 10.1093/annonc/mdw008
PG 7
WC Oncology
SC Oncology
GA DJ5HO
UT WOS:000374237700020
PM 26802155
ER
EF